pubblicazioni

@article{pmid18218852,

title = {Altered intracellular and extracellular signaling leads to impaired Ŧ-cell functions in AĐA-SCIĐ patients},

author = {B Cassani and M Mirolo and F Cattaneo and U Benninghoff and M Hershfield and F Carlucci and A Tabucchi and C Bordignon and M G Roncarolo and A Aiuti},

year  = {2008},

date = {2008-01-01},

journal = {Blood},

volume = {111},

number = {8},

pages = {4209--4219},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Zoledziewska2008-oq,

title = {Further evidence of a primary, causal association of the  PTPN22 620W variant with type 1 diabetes},

author = {Magdalena Zoledziewska and Chiara Perra and Valeria Orr`u and Loredana Moi and Paola Frongia and Mauro Congia and Nunzio Bottini and Francesco Cucca},

doi = {10.2337/db07-0289},

year  = {2008},

date = {2008-01-01},

urldate = {2008-01-01},

journal = {Diabetes},

volume = {57},

number = {1},

pages = {229--234},

publisher = {Ämerican Diabetes Association},

abstract = {ÖBJECTIVE: The minor allele of the nonsynonymous single 

 nucleotide polymorphism (SNP) +1858C>T within the PTPN22 gene is 

 positively associated with type 1 diabetes and other autoimmune 

 diseases. Genetic and functional data underline its causal 

 effect, but some studies suggest that this polymorphism does not 

 entirely explain disease association of the PTPN22 region. The 

 aim of this study was to evaluate type 1 diabetes association 

 within this gene in the Sardinian population. RESEARCH DESIGN 

 AND METHODS: We resequenced the exons and potentially relevant 

 portions of PTPN22 and detected 24 polymorphisms (23 SNPs and 1 

 deletion insertion polymorphism [DIP]), 8 of which were novel. A 

 representative set of 14 SNPs and the DIP were sequentially 

 genotyped and assessed for disease association in 794 families, 

 490 sporadic patients, and 721 matched control subjects. 

 RESULTS: The +1858C>T variant, albeit rare in the general 

 Sardinian population (allele frequency 0.014), was positively associated with type 1 diabetes (P(one tail) = 3.7 x 10(-3)). In 

 contrast, the background haplotype in which this mutation 

 occurred was common (haplotype frequency 0.117) and neutrally 

 associated with disease. We did not confirm disease associations 

 reported in other populations for non +1858C>T variants 

 (rs2488457, rs1310182, and rs3811021), although they were 

 present in appreciable frequencies in Sardinia. Additional weak 

 disease associations with rare variants were detected in the 

 Sardinian families but not confirmed in independent case-control 

 sample sets and are most likely spurious. CONCLUSIONS: We 

 provide further evidence that the +1858C>T polymorphism is 

 primarily associated with type 1 diabetes and exclude major 

 contributions from other purportedly relevant variants within 

 this gene."},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{schirru_decline_2007,

title = {Decline of lactase activity and c/t-13910 variant in Sardinian childhood.},

author = {Schirru, Enrico and Corona, Valeria and Usai-Satta, Paolo and Scarpa, Maria and Cucca, Francesco and De Virgiliis, Stefano and Rossino, Rossano and Frau, Fulvia and Macis, Maria Doloretta and Jores, Rita-Desiree and Congia, Mauro},

doi = {10.1097/MPG.0b013e31805b5899},

issn = {1536-4801 0277-2116},

year  = {2007},

date = {2007-10-01},

journal = {J Pediatr Gastroenterol Nutr},

volume = {45},

number = {4},

pages = {503--506},

abstract = {OBJECTIVES: Our study aims to determine the age of onset of adult-type hypolactasia in Sardinians, and to establish the age at which genotyping of the C/T-13910 variant can be used reliably in the diagnosis of lactose malabsorption. PATIENTS AND METHODS: A lactose breath hydrogen test was given to 383 randomly selected patients, from 3 to 19 years old. RESULTS: The C/C-13910 genotype was found in 90% of patients; the frequency of the positive lactose breath hydrogen test increased with age and reached a prevalence of 85% at 9 years. CONCLUSIONS: In Sardinians, adult-type hypolactasia becomes phenotypically evident in all individuals older than 9 years, suggesting that this should be considered the minimum age at which the genetic test for lactase nonpersistence should be applied.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{schirru_genetic_2007,

title = {Genetic testing improves the diagnosis of adult type hypolactasia in the Mediterranean population of Sardinia.},

author = {Schirru, E. and Corona, V. and Usai-Satta, P. and Scarpa, M. and Oppia, F. and Loriga, F. and Cucca, F. and De Virgiliis, S. and Rossino, R. and Macis, M. Doloretta and Jores, R.-D. and Congia, M.},

doi = {10.1038/sj.ejcn.1602638},

issn = {0954-3007 0954-3007},

year  = {2007},

date = {2007-10-01},

journal = {Eur J Clin Nutr},

volume = {61},

number = {10},

pages = {1220--1225},

abstract = {OBJECTIVE: Recently, the C/T-13910 polymorphism on chromosome 2q21 in North-European populations has been found completely associated with lactase activity and its genetic typing proposed as first-stage screening test for adult hypolactasia. However, the C/T-13910 variant in some sub-Saharan African groups is not a predictor of lactase persistence. In this work, we wanted to verify if in the Mediterranean island of Sardinia, located in Southern Europe, the C/T-13910 polymorphism may be useful or not for the diagnosis of adult type hypolactasia. DESIGN: Validation study of a genetic testing for adult type hypolactasia in Sardinians. SETTING: Brotzu Hospital and Microcitemico Hospital, Cagliari, Italy. SUBJECTS: The sample consisted in 84 Sardinian individuals (63 women and 21 men; range 20-73 years) selected from a group of 832 patients. METHODS: Genetic testing was compared to an improved test obtained by a combination of different breath hydrogen tests and clinical assessment. RESULTS: We found that all 49 individuals with lactose malabsorption, demonstrated by a combination of different breath hydrogen tests and clinical assessment, carried the C/C-13910 genotype associated with lactase non-persistence, 23 individuals with lactose normal absorption carried the C/T-13910 genotype associated with lactase persistence and only one person with the above phenotype showed a discordant C/C-13910 genotype. The genetic testing showed very high sensitivity, specificity, positive and negative predictive values of 100, 95.8, 98 and 100%, respectively. CONCLUSIONS: Sardinians, unlike some ethnic groups in sub-Saharan Africa, show the same genetic association of hypolactasia with the C/T-13910 variant as other North-European populations. The genetic testing for the C/T-13910 variant may contribute to improving the diagnosis of adult type hypolactasia.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{thomson_relative_2007,

title = {Relative predispositional effects of HLA class II DRB1-DQB1 haplotypes and genotypes on type 1 diabetes: a meta-analysis.},

author = {Thomson, G. and Valdes, A. M. and Noble, J. A. and Kockum, I. and Grote, M. N. and Najman, J. and Erlich, H. A. and Cucca, F. and Pugliese, A. and Steenkiste, A. and Dorman, J. S. and Caillat-Zucman, S. and Hermann, R. and Ilonen, J. and Lambert, A. P. and Bingley, P. J. and Gillespie, K. M. and Lernmark, A. and Sanjeevi, C. B. and Ronningen, K. S. and Undlien, D. E. and Thorsby, E. and Petrone, A. and Buzzetti, R. and Koeleman, B. P. C. and Roep, B. O. and Saruhan-Direskeneli, G. and Uyar, F. A. and Gunoz, H. and Gorodezky, C. and Alaez, C. and Boehm, B. O. and Mlynarski, W. and Ikegami, H. and Berrino, M. and Fasano, M. E. and Dametto, E. and Israel, S. and Brautbar, C. and Santiago-Cortes, A. and Frazer de Llado, T. and She, J.-X. and Bugawan, T. L. and Rotter, J. I. and Raffel, L. and Zeidler, A. and Leyva-Cobian, F. and Hawkins, B. R. and Chan, S. H. and Castano, L. and Pociot, F. and Nerup, J.},

doi = {10.1111/j.1399-0039.2007.00867.x},

issn = {0001-2815 0001-2815},

year  = {2007},

date = {2007-08-01},

journal = {Tissue Antigens},

volume = {70},

number = {2},

pages = {110--127},

abstract = {The direct involvement of the human leukocyte antigen class II DR-DQ genes in type 1 diabetes (T1D) is well established, and these genes display a complex hierarchy of risk effects at the genotype and haplotype levels. We investigated, using data from 38 studies, whether the DR-DQ haplotypes and genotypes show the same relative predispositional effects across populations and ethnic groups. Significant differences in risk within a population were considered, as well as comparisons across populations using the patient/control (P/C) ratio. Within a population, the ratio of the P/C ratios for two different genotypes or haplotypes is a function only of the absolute penetrance values, allowing ranking of risk effects. Categories of consistent predisposing, intermediate ('neutral'), and protective haplotypes were identified and found to correlate with disease prevalence and the marked ethnic differences in DRB1-DQB1 frequencies. Specific effects were identified, for example for predisposing haplotypes, there was a statistically significant and consistent hierarchy for DR4 DQB1*0302s: DRB1*0405 =*0401 =*0402 textgreater *0404 textgreater *0403, with DRB1*0301 DQB1*0200 (DR3) being significantly less predisposing than DRB1*0402 and more than DRB1*0404. The predisposing DRB1*0401 DQB1*0302 haplotype was relatively increased compared with the protective haplotype DRB1*0401 DQB1*0301 in heterozygotes with DR3 compared with heterozygotes with DRB1*0101 DQB1*0501 (DR1). Our results show that meta-analyses and use of the P/C ratio and rankings thereof can be valuable in determining T1D risk factors at the haplotype and amino acid residue levels.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{sellaroli_shared_2007,

title = {Shared genetic data and the rights of involved people.},

author = {Sellaroli, Valentina and Cucca, Francesco and Santosuosso, Amedeo},

issn = {1134-7198 1134-7198},

year  = {2007},

date = {2007-06-01},

journal = {Rev Derecho Genoma Hum},

number = {26},

pages = {193--231},

abstract = {The authors examine the two main attitudes toward genetics: Exceptionalism and Undervaluation. They firstly pose the basis of the matter from the scientific point of view and then verify how these two attitudes really work in the different fields where human genetics finds relevant applications, dealing with the questions arising from the unique characteristics of genetic data that is shared among the whole bio-group. Then some judicial cases related to the conflicts arising when genetic data are stored in repositories, whatever the aims and reasons, are presented and discussed. The matter is then considered from the criminal law perspective, in the light of the new possible implications of DNA fingerprinting in criminal investigations. Finally, some general considerations on opposing Exceptionalism/Undervaluation viewpoints and the real reason for making up new rules are presented.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{bonfigli_high_2007,

title = {High frequency of the TCRBV20S1 null allele in the Sardinian population.},

author = {Bonfigli, Silvana and Fozza, Claudio and Contini, Salvatore and Buzzetti, Raffaella and Cucca, Francesco and Longinotti, Maurizio},

doi = {10.1016/j.humimm.2007.01.011},

issn = {0198-8859 0198-8859},

year  = {2007},

date = {2007-05-01},

journal = {Hum Immunol},

volume = {68},

number = {5},

pages = {426--429},

abstract = {Single nucleotide polymorphisms (SNPs) in the T-cell receptor (TCR) gene segments might play a role in shaping the TCR repertoire. Three polymorphisms have been described for the TCRBV20S1 gene segment, one of which is responsible for a nucleotide substitution at position 524, resulting in the introduction of a stop codon. Individuals homozygous for this inactivating polymorphism ("null allele") are unable to express TCRBV20 gene products. Using DNA restriction digestion analysis, we investigated the frequency of this polymorphism in 111 healthy Sardinian subjects. Inhabitants of the Mediterranean island of Sardinia are considered to represent a genetically isolated population. Our analyses revealed an incidence of 19.8% of homozygosity for the null allele, corresponding to an allele frequency of 0.45. Such an incidence, significantly higher than the one detected in 83 non-Sardinian Caucasians (6%), is the most elevated so far reported in the literature. BV20 is a single member subfamily and the null allele produces a gap in the potential TCR repertoire. Therefore, it is possible that an undetermined selective pressure could have played a role in determining the high frequency of this inactivating polymorphism in Sardinians. Alternatively, this finding could be related to a founder effect in this ancient island population.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{marrosu_variation_2007,

title = {Variation of the myelin oligodendrocyte glycoprotein gene is not primarily associated with multiple sclerosis in the Sardinian population.},

author = {Marrosu, Maria Giovanna and Murru, Raffaele and Costa, Gianna and Melis, Maria Cristina and Rolesu, Marcella and Schirru, Lucia and Solla, Elisabetta and Cuccu, Stefania and Secci, Maria Antonietta and Whalen, Michael B. and Cocco, Eleonora and Pugliatti, Maura and Sotgiu, Stefano and Rosati, Giulio and Cucca, Francesco},

doi = {10.1186/1471-2156-8-25},

issn = {1471-2156 1471-2156},

year  = {2007},

date = {2007-05-01},

journal = {BMC Genet},

volume = {8},

pages = {25},

abstract = {BACKGROUND: Multiple sclerosis (MS) is consistently associated with particular},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid17476358,

title = {A hypomorphic R229Q Rag2 mouse mutant recapitulates human Omenn syndrome},

author = {V Marrella and P L Poliani and A Casati and F Rucci and L Frascoli and M L Gougeon and B Lemercier and M Bosticardo and M Ravanini and M Battaglia and M G Roncarolo and M Cavazzana-Calvo and F Facchetti and L D Notarangelo and P Vezzoni and F Grassi and A Villa},

year  = {2007},

date = {2007-05-01},

journal = {J Clin Invest},

volume = {117},

number = {5},

pages = {1260--1269},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid17273969,

title = {Mutations in cohesin complex members SMC3 and SMC1A cause a mild variant of cornelia de Lange syndrome with predominant mental retardation},

author = {M A Deardorff and M Kaur and D Yaeger and A Rampuria and S Korolev and J Pie and C Gil-Rodríguez and M Arnedo and B Loeys and A D Kline and M Wilson and K Lillquist and V Siu and F J Ramos and A Musio and L S Jackson and D Dorsett and I D Krantz},

year  = {2007},

date = {2007-03-01},

volume = {80},

number = {3},

pages = {485--494},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{jores_hla-dqb1*0201_2007,

title = {HLA-DQB1*0201 homozygosis predisposes to severe intestinal damage in celiac disease.},

author = {Jores, Rita-Desiree and Frau, Fulvia and Cucca, Francesco and Grazia Clemente, Maria and Orru, Sandra and Rais, Marco and De Virgiliis, Stefano and Congia, Mauro},

doi = {10.1080/00365520600789859},

issn = {0036-5521 0036-5521},

year  = {2007},

date = {2007-01-01},

journal = {Scand J Gastroenterol},

volume = {42},

number = {1},

pages = {48--53},

abstract = {OBJECTIVE: Celiac disease (CD) is a T-lymphocyte-mediated small intestinal enteropathy triggered and maintained by dietary gluten, with a strong genetic component mapping to the HLA genes encoding for the class II DQ(alpha1*0501, beta1*02) molecule. Damage of the small intestine may cause a variety of clinical signs ranging from isolated long-standing iron-deficiency anemia refractory to iron supplementation to forms of severe malnutrition that may become life threatening. However, patients carrying the typical intestinal lesions of CD and presenting no symptoms at all (silent CD) are also a common clinical observation. Since it is commonly assumed that clinical signs and symptoms tend to correlate with the severity of the intestinal damage, the purpose of this study was to investigate whether particular HLA class II genotypes might also influence the extent of intestinal damage and consequently the clinical presentation of the disease. MATERIAL AND METHODS: We retrospectively compared histological grading of celiac disease intestinal biopsies with HLA haplotype, age at onset of disease and clinical signs and symptoms. RESULTS: Our findings showed that homozygosis for the DQB1*0201 allele is associated with a higher severity of the histological score (ptextless0.008). Of note for the clinician, this work also suggests that the same type 3c of intestinal damage causes a different clinical syndrome, depending on the patient's age. CONCLUSIONS: The genetic predisposition at the HLA-DQB1 locus influences the severity of the mucosal damage in a dose-dependent manner, but not the clinical presentation, of celiac disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{balaci_irak-m_2007,

title = {IRAK-M is involved in the pathogenesis of early-onset persistent asthma.},

author = {Balaci, Lenuta and Spada, Maria Cristina and Olla, Nazario and Sole, Gabriella and Loddo, Laura and Anedda, Francesca and Naitza, Silvia and Zuncheddu, Maria Antonietta and Maschio, Andrea and Altea, Daniele and Uda, Manuela and Pilia, Sabrina and Sanna, Serena and Masala, Marco and Crisponi, Laura and Fattori, Matilde and Devoto, Marcella and Doratiotto, Silvia and Rassu, Stefania and Mereu, Simonetta and Giua, Enrico and Cadeddu, Natalina Graziella and Atzeni, Roberto and Pelosi, Umberto and Corrias, Adriano and Perra, Roberto and Torrazza, Pier Luigi and Pirina, Pietro and Ginesu, Francesco and Marcias, Silvano and Schintu, Maria Grazia and Del Giacco, Gennaro Sergio and Manconi, Paolo Emilio and Malerba, Giovanni and Bisognin, Andrea and Trabetti, Elisabetta and Boner, Attilio and Pescollderungg, Lydia and Pignatti, Pier Franco and Schlessinger, David and Cao, Antonio and Pilia, Giuseppe},

doi = {10.1086/518259},

issn = {0002-9297 0002-9297},

year  = {2007},

date = {2007-01-01},

journal = {Am J Hum Genet},

volume = {80},

number = {6},

pages = {1103--1114},

abstract = {Asthma is a multifactorial disease influenced by genetic and environmental factors. In the past decade, several loci and textgreater100 genes have been found to be associated with the disease in at least one population. Among these loci, region 12q13-24 has been implicated in asthma etiology in multiple populations, suggesting that it harbors one or more asthma susceptibility genes. We performed linkage and association analyses by transmission/disequilibrium test and case-control analysis in the candidate region 12q13-24, using the Sardinian founder population, in which limited heterogeneity of pathogenetic alleles for monogenic and complex disorders as well as of environmental conditions should facilitate the study of multifactorial traits. We analyzed our cohort, using a cutoff age of 13 years at asthma onset, and detected significant linkage to a portion of 12q13-24. We identified IRAK-M as the gene contributing to the linkage and showed that it is associated with early-onset persistent asthma. We defined protective and predisposing SNP haplotypes and replicated associations in an outbred Italian population. Sequence analysis in patients found mutations, including inactivating lesions, in the IRAK-M coding region. Immunohistochemistry of lung biopsies showed that IRAK-M is highly expressed in epithelial cells. We report that IRAK-M is involved in the pathogenesis of early-onset persistent asthma. IRAK-M, a negative regulator of the Toll-like receptor/IL-1R pathways, is a master regulator of NF- kappa B and inflammation. Our data suggest a mechanistic link between hyperactivation of the innate immune system and chronic airway inflammation and indicate IRAK-M as a potential target for therapeutic intervention against asthma.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{crisponi_crisponi_2007,

title = {Crisponi syndrome is caused by mutations in the CRLF1 gene and is allelic to cold-induced sweating syndrome type 1.},

author = {Crisponi, Laura and Crisponi, Giangiorgio and Meloni, Alessandra and Toliat, Mohammad Reza and Nurnberg, Gudrun and Usala, Gianluca and Uda, Manuela and Masala, Marco and Hohne, Wolfgang and Becker, Christian and Marongiu, Mara and Chiappe, Francesca and Kleta, Robert and Rauch, Anita and Wollnik, Bernd and Strasser, Friedrich and Reese, Thomas and Jakobs, Cornelis and Kurlemann, Gerd and Cao, Antonio and Nurnberg, Peter and Rutsch, Frank},

doi = {10.1086/516843},

issn = {0002-9297 0002-9297},

year  = {2007},

date = {2007-01-01},

journal = {Am J Hum Genet},

volume = {80},

number = {5},

pages = {971--981},

abstract = {Crisponi syndrome is a severe autosomal recessive condition that is phenotypically characterized by abnormal, paroxysmal muscular contractions resembling neonatal tetanus, large face, broad nose, anteverted nares, camptodactyly, hyperthermia, and sudden death in most cases. We performed homozygosity mapping in five Sardinian and three Turkish families with Crisponi syndrome, using high-density single-nucleotide polymorphism arrays, and identified a critical region on chromosome 19p12-13.1. The most prominent candidate gene was CRLF1, recently found to be involved in the pathogenesis of cold-induced sweating syndrome type 1 (CISS1). CISS1 belongs to a group of conditions with overlapping phenotypes, also including cold-induced sweating syndrome type 2 and Stuve-Wiedemann syndrome. All these syndromes are caused by mutations of genes of the ciliary neurotrophic factor (CNTF)-receptor pathway. Here, we describe the identification of four different CRLF1 mutations in eight different Crisponi-affected families, including a missense mutation, a single-nucleotide insertion, and a nonsense and an insertion/deletion (indel) mutation, all segregating with the disease trait in the families. Comparison of the mutation spectra of Crisponi syndrome and CISS1 suggests that neither the type nor the location of the CRLF1 mutations points to a phenotype/genotype correlation that would account for the most severe phenotype in Crisponi syndrome. Other, still-unknown molecular factors may be responsible for the variable phenotypic expression of the CRLF1 mutations. We suggest that the syndromes can comprise a family of "CNTF-receptor-related disorders," of which Crisponi syndrome would be the newest member and allelic to CISS1.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid17632511,

title = {Osteoclast-poor human osteopetrosis due to mutations in the gene encoding RANKL},

author = {C Sobacchi and A Frattini and M M Guerrini and M Abinun and A Pangrazio and L Susani and R Bredius and G Mancini and A Cant and N Bishop and P Grabowski and A Del Fattore and C Messina and G Errigo and F P Coxon and D I Scott and A Teti and M J Rogers and P Vezzoni and A Villa and M H Helfrich},

year  = {2007},

date = {2007-01-01},

journal = {Nat Genet},

volume = {39},

number = {8},

pages = {960--962},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid17671653,

title = {Multilineage hematopoietic reconstitution without clonal selection in AĐA-SCIĐ patients treated with stem cell gene therapy},

year  = {2007},

date = {2007-01-01},

journal = {J Clin Invest},

volume = {117},

number = {8},

pages = {2233--2240},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{orofino_no_2006,

title = {No influence of chromosome Y haplogroup variation in acute graft-versus-host disease in sardinia.},

author = {Orofino, Maria Grazia and Contu, Daniela and Argiolu, Francesca and Sanna, Maria Adele and Gaziev, Javid and La Nasa, Giorgio and Vacca, Adriana and Cao, Antonio and Cucca, Francesco},

doi = {10.1097/01.tp.0000235822.46197.61},

issn = {0041-1337 0041-1337},

year  = {2006},

date = {2006-12-01},

journal = {Transplantation},

volume = {82},

number = {11},

pages = {1529--1532},

abstract = {The donor-recipient sex-related mismatch has been reported as a risk factor for acute graft-versus-host disease (GVHD). However, the results obtained in previous studies appear to be contradictory. Here we evaluate the impact of donor-recipient sex-related mismatch in a series of 204 Sardinian individuals (92.1% of them affected by Beta- Thalassemia major) who underwent bone marrow transplantation (BMT) from human leukocyte antigen (HLA) identical siblings. In all, 78 of these patients had acute GVHD (aGVHD). We found that also in this homogenous group of patients from a homogenous population, the donor-female/recipient-male pair provided an increased risk for aGVHD when compared with a reference donor-male/recipient-male pair (POR=2.3},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid16931591,

title = {A new insertion/deletion of the cystic fibrosis transmembrane conductance regulator gene accounts for 3.4% of cystic fibrosis mutations in Sardinia: implications for population screening},

author = { V. Faà and P. P. Bettoli and M. Demurtas and M. Zanda and V. Ferri and A. Cao and M. C. Rosatelli},

year  = {2006},

date = {2006-09-01},

journal = {J Mol Diagn},

volume = {8},

number = {4},

pages = {499--503},

abstract = {Previous studies performed on Sardinian patients affected by cystic fibrosis (CF) have led to the identification of molecular defects in 87 of 88 patients. Two mutations, the F508del and T338I, were quite prevalent and accounted for 50% and 20% of the molecular defects, respectively. T338I has been detected rarely in other populations, most likely because of the genetic isolation of Sardinians. In the present study, we have performed a molecular analysis of the CF gene in eight Sardinian patients in whom only a single mutation has been defined. Using DNA analyses (Southern blot, single nucleotide polymorphisms, microsatellite analyses, and Extra-Long polymerase chain reaction) selected to detect gross gene rearrangement and by using mRNA studies, we detected a novel mutation c.54-5811_164 + 2186del8108ins182 in six of the eight patients investigated. This mutation consists of a gross deletion of 8108 bp spanning exon 2 with an insertion of 182 bp at the deletion junction, between nucleotide 54-5811 of intron 1 (IVS1 nt16864) and nucleotide 164 + 2186 of intron 2 (IVS2 nt 2186). By including the novel mutation in our mutation panel we are now able to reach a 95% detection rate, thereby improving the process of carrier detection and genetic counseling in Sardinia.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bottini2006,

title = {Role of PTPN22 in type 1 diabetes and other autoimmune diseases},

author = {Bottini, Nunzio and Vang, Torkel and Cucca, Francesco and Mustelin, Tomas},

url = {http://www.ncbi.nlm.nih.gov/pubmed/16697661 http://linkinghub.elsevier.com/retrieve/pii/S1044532306000455},

doi = {10.1016/j.smim.2006.03.008},

issn = {10445323},

year  = {2006},

date = {2006-08-01},

journal = {Seminars in Immunology},

volume = {18},

number = {4},

pages = {207--213},

abstract = {We recently discovered that a single-nucleotide polymorphism (SNP) in the lymphoid tyrosine phosphatase (LYP), encoded by the PTPN22 gene on chromosome 1p13, correlates strongly with the incidence of type 1 diabetes (T1D) in two independent populations. This findings has now been verified by numerous studies and it has been expanded to rheumatoid arthritis, juvenile rheumatoid arthritis, systemic lupus erythematosus, Graves' disease, generalized vitiligo and other autoimmune disease. Here we review the genetics of the SNP and its association with autoimmunity, discuss the function of the phosphatase in signaling, the biochemistry of the disease-predisposing allele, and the possible mechanisms by which PTPN22 contributes to the development of human disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid16813530,

title = {Mutations in OSŦM1 (grey lethal) define a particularly severe form of autosomal recessive osteopetrosis with neural involvement},

author = {A Pangrazio and P L Poliani and A Megarbane and G Lefranc and E Lanino and M Di Rocco and F Rucci and F Lucchini and M Ravanini and F Facchetti and M Abinun and P Vezzoni and A Villa and A Frattini},

year  = {2006},

date = {2006-07-01},

journal = {J Bone Miner Res},

volume = {21},

number = {7},

pages = {1098--1105},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid16769824,

title = {Nebulin-deficient mice exhibit shorter thin filament lengths and reduced contractile function in skeletal muscle},

author = {M L Bang and X Li and R Littlefield and S Bremner and A Thor and K U Knowlton and R L Lieber and J Chen},

year  = {2006},

date = {2006-06-01},

journal = {J Cell Biol},

volume = {173},

number = {6},

pages = {905--916},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{sapone_zonulin_2006,

title = {Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives.},

author = {Sapone, Anna and de Magistris, Laura and Pietzak, Michelle and Clemente, Maria G. and Tripathi, Amit and Cucca, Francesco and Lampis, Rosanna and Kryszak, Deborah and Carteni, Maria and Generoso, Maddalena and Iafusco, Dario and Prisco, Francesco and Laghi, Francesca and Riegler, Gabriele and Carratu, Romano and Counts, Debra and Fasano, Alessio},

issn = {0012-1797 0012-1797},

year  = {2006},

date = {2006-05-01},

journal = {Diabetes},

volume = {55},

number = {5},

pages = {1443--1449},

abstract = {Zonulin, a protein that modulates intestinal permeability, is upregulated in several autoimmune diseases and is involved in the pathogenesis of autoimmune diabetes in the BB/Wor animal model of the disease. To verify the association between serum zonulin levels and in vivo intestinal permeability in patients with type 1 diabetes, both parameters were investigated in different stages of the autoimmune process. Forty-two percent (141 of 339) of the patients had abnormal serum zonulin levels, as compared with age-matched control subjects. The increased zonulin levels correlated with increased intestinal permeability in vivo and changes in claudin-1, claudin-2, and myosin IXB genes expression, while no changes were detected in ZO1 and occludin genes expression. When tested in serum samples collected during the pre-type 1 diabetes phase, elevated serum zonulin was detected in 70% of subjects and preceded by 3.5 +/- 0.9 years the onset of the disease in those patients who went on to develop type 1 diabetes. Combined, these results suggest that zonulin upregulation is associated with increased intestinal permeability in a subgroup of type 1 diabetic patients. Zonulin upregulation seems to precede the onset of the disease, providing a possible link between increased intestinal permeability, environmental exposure to non-self antigens, and the development of autoimmunity in genetically susceptible individuals.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid16604071,

title = {X-linked Cornelia de Lange syndrome owing to SMC1L1 mutations},

author = {A Musio and A Selicorni and M L Focarelli and C Gervasini and D Milani and S Russo and P Vezzoni and L Larizza},

year  = {2006},

date = {2006-05-01},

journal = {Nat Genet},

volume = {38},

number = {5},

pages = {528--530},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid16445840,

title = {Thalassaemia-like carriers not linked to the beta-globin gene cluster},

author = { V. Faà and A. Meloni and L. Moi and G. Ibba and M. Travi and A. Vitucci and A. Cao and M. C. Rosatelli},

year  = {2006},

date = {2006-03-01},

journal = {Br J Haematol},

volume = {132},

number = {5},

pages = {640--650},

abstract = {This study describes the largest series reported to date, of individuals belonging to unrelated families carrying a beta-thalassaemia-like phenotype in whom the beta-globin gene was found to be structurally intact by sequence analysis. This genetic determinant appears haematologically heterogeneous, displaying either a silent beta-thalassaemia-like phenotype or a typical beta-thalassaemia carrier-like phenotype in different families. Compound heterozygosity for both beta-thalassaemia-like determinant and typical beta-thalassaemia allele resulted either in thalassaemia intermedia or thalassaemia major. By linkage analysis both the silent and the typical beta-like determinants were found not to be linked to the beta-globin cluster. Sequence analysis of the hypersensitive site cores of locus control region and of the genes coding for the transcription factors erythroid Kruppel-like factor and nuclear factor (erythroid-derived 2) were normal. beta-globin mRNA levels determined by real-time polymerase chain reaction were reduced in both types of beta-like carriers. These results indicate the existence of causative genetic determinants not yet molecularly defined, but most likely, resulting from either the reduction or loss of function of a gene coding for unknown transcriptional regulator(s) of the beta-globin gene. The knowledge of these rare beta-thalassaemia-like determinants have implications for clinical and, especially, prenatal diagnosis of beta-thalassaemia.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pilia_heritability_2006,

title = {Heritability of cardiovascular and personality traits in 6,148 Sardinians.},

author = {Pilia, Giuseppe and Chen, Wei-Min and Scuteri, Angelo and Orru, Marco and Albai, Giuseppe and Dei, Mariano and Lai, Sandra and Usala, Gianluca and Lai, Monica and Loi, Paola and Mameli, Cinzia and Vacca, Loredana and Deiana, Manila and Olla, Nazario and Masala, Marco and Cao, Antonio and Najjar, Samer S. and Terracciano, Antonio and Nedorezov, Timur and Sharov, Alexei and Zonderman, Alan B. and Abecasis, Goncalo R. and Costa, Paul and Lakatta, Edward and Schlessinger, David},

doi = {10.1371/journal.pgen.0020132},

issn = {1553-7404 1553-7390},

year  = {2006},

date = {2006-01-01},

journal = {PLoS Genet},

volume = {2},

number = {8},

pages = {e132},

abstract = {In family studies, phenotypic similarities between relatives yield information on the overall contribution of genes to trait variation. Large samples are important for these family studies, especially when comparing heritability between subgroups such as young and old, or males and females. We recruited a cohort of 6,148 participants, aged 14-102 y, from four clustered towns in Sardinia. The cohort includes 34,469 relative pairs. To extract genetic information, we implemented software for variance components heritability analysis, designed to handle large pedigrees, analyze multiple traits simultaneously, and model heterogeneity. Here, we report heritability analyses for 98 quantitative traits, focusing on facets of personality and cardiovascular function. We also summarize results of bivariate analyses for all pairs of traits and of heterogeneity analyses for each trait. We found a significant genetic component for every trait. On average, genetic effects explained 40% of the variance for 38 blood tests, 51% for five anthropometric measures, 25% for 20 measures of cardiovascular function, and 19% for 35 personality traits. Four traits showed significant evidence for an X-linked component. Bivariate analyses suggested overlapping genetic determinants for many traits, including multiple personality facets and several traits related to the metabolic syndrome; but we found no evidence for shared genetic determinants that might underlie the reported association of some personality traits and cardiovascular risk factors. Models allowing for heterogeneity suggested that, in this cohort, the genetic variance was typically larger in females and in younger individuals, but interesting exceptions were observed. For example, narrow heritability of blood pressure was approximately 26% in individuals more than 42 y old, but only approximately 8% in younger individuals. Despite the heterogeneity in effect sizes, the same loci appear to contribute to variance in young and old, and in males and females. In summary, we find significant evidence for heritability of many medically important traits, including cardiovascular function and personality. Evidence for heterogeneity by age and sex suggests that models allowing for these differences will be important in mapping quantitative traits.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Vang2005,

title = {Autoimmune-associated lymphoid tyrosine phosphatase is a gain-of-function variant.},

author = {Vang, Torkel and Congia, Mauro and Macis, Maria Doloretta and Musumeci, Lucia and Orr{ú}, Valeria and Zavattari, Patrizia and Nika, Konstantina and Tautz, Lutz and Task{é}n, Kjetil and Cucca, Francesco and Mustelin, Tomas and Bottini, Nunzio},

url = {http://www.nature.com/doifinder/10.1038/ng1673 http://www.ncbi.nlm.nih.gov/pubmed/16273109},

doi = {10.1038/ng1673},

issn = {1061-4036},

year  = {2005},

date = {2005-12-01},

journal = {Nature genetics},

volume = {37},

number = {12},

pages = {1317--9},

abstract = {A SNP in the gene PTPN22 is associated with type 1 diabetes, rheumatoid arthritis, lupus, Graves thyroiditis, Addison disease and other autoimmune disorders. T cells from carriers of the predisposing allele produce less interleukin-2 upon TCR stimulation, and the encoded phosphatase has higher catalytic activity and is a more potent negative regulator of T lymphocyte activation. We conclude that the autoimmune-predisposing allele is a gain-of-function mutant.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{vang_autoimmune-associated_2005,

title = {Autoimmune-associated lymphoid tyrosine phosphatase is a gain-of-function variant.},

author = {Vang, Torkel and Congia, Mauro and Macis, Maria Doloretta and Musumeci, Lucia and Orru, Valeria and Zavattari, Patrizia and Nika, Konstantina and Tautz, Lutz and Tasken, Kjetil and Cucca, Francesco and Mustelin, Tomas and Bottini, Nunzio},

doi = {10.1038/ng1673},

issn = {1061-4036 1061-4036},

year  = {2005},

date = {2005-12-01},

journal = {Nat Genet},

volume = {37},

number = {12},

pages = {1317--1319},

abstract = {A SNP in the gene PTPN22 is associated with type 1 diabetes, rheumatoid arthritis, lupus, Graves thyroiditis, Addison disease and other autoimmune disorders. T cells from carriers of the predisposing allele produce less interleukin-2 upon TCR stimulation, and the encoded phosphatase has higher catalytic activity and is a more potent negative regulator of T lymphocyte activation. We conclude that the autoimmune-predisposing allele is a gain-of-function mutant.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Vang2005-xl,

title = {Äutoimmune-associated lymphoid tyrosine phosphatase is a  gain-of-function variant},

author = {Torkel Vang and Mauro Congia and Maria Doloretta Macis and Lucia Musumeci and Valeria Orr'u and Patrizia Zavattari and Konstantina Nika and Lutz Tautz and Kjetil Taskén and Francesco Cucca and Tomas Mustelin and Nunzio Bottini},

doi = {10.1038/ng1673},

year  = {2005},

date = {2005-12-01},

urldate = {2005-12-01},

journal = {Nat. Genet.},

volume = {37},

number = {12},

pages = {1317--1319},

publisher = {Springer Science and Business Media LLC},

abstract = {Ä SNP in the gene PTPN22 is associated with type 1 diabetes, 

 rheumatoid arthritis, lupus, Graves thyroiditis, Addison disease 

 and other autoimmune disorders. T cells from carriers of the 

 predisposing allele produce less interleukin-2 upon TCR 

 stimulation, and the encoded phosphatase has higher catalytic 

 activity and is a more potent negative regulator of T lymphocyte 

 activation. We conclude that the autoimmune-predisposing allele 

 is a gain-of-function mutant."},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid16195375,

title = {Rescue of AŦPa3-deficient murine malignant osteopetrosis by hematopoietic stem cell transplantation in utero},

author = {A Frattini and H C Blair and M G Sacco and F Cerisoli and F Faggioli and E M Catò and A Pangrazio and A Musio and F Rucci and C Sobacchi and A C Sharrow and S E Kalla and M G Bruzzone and R Colombo and M C Magli and P Vezzoni and A Villa},

year  = {2005},

date = {2005-01-01},

journal = {Proc Natl Acad Sci U S A},

volume = {102},

number = {41},

pages = {14629--14634},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid15837556,

title = {C1-inhibitor protects against brain ischemia-reperfusion injury via inhibition of cell recruitment and inflammation},

author = {C Storini and E Rossi and V Marrella and M Distaso and R Veerhuis and C Vergani and L Bergamaschini and M G De Simoni},

year  = {2005},

date = {2005-01-01},

journal = {Neurobiol Dis},

volume = {19},

number = {1-2},

pages = {10--17},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Marrosu2004,

title = {The co-inheritance of type 1 diabetes and multiple sclerosis in Sardinia cannot be explained by genotype variation in the HLA region alone.},

author = {Marrosu, Maria Giovanna and Motzo, Costantino and Murru, Raffaele and Lampis, Rosanna and Costa, Gianna and Zavattari, Patrizia and Contu, Daniela and Fadda, Elisabetta and Cocco, Eleonora and Cucca, Francesco},

url = {https://academic.oup.com/hmg/article-lookup/doi/10.1093/hmg/ddh319 http://www.ncbi.nlm.nih.gov/pubmed/15471889},

doi = {10.1093/hmg/ddh319},

issn = {0964-6906},

year  = {2004},

date = {2004-12-01},

journal = {Human molecular genetics},

volume = {13},

number = {23},

pages = {2919--24},

abstract = {Type 1 diabetes (T1D) and multiple sclerosis (MS) are two autoimmune diseases which exhibit a considerably higher incidence in Sardinia compared with the surrounding southern European populations. Surprisingly, a 5-fold increased prevalence of T1D has also been observed in Sardinian MS patients. Susceptibility to both disorders is associated with common variants of the HLA-DRB1 and -DQB1 loci. In this study, we determined the relative contribution of genotype variation of these loci to the co-occurrence of the two disorders in Sardinia. We genotyped 1052 T1D patients and 1049 MS patients (31 of whom also had T1D) together with 1917 ethnically matched controls. On the basis of the absolute risks for T1D of the HLA-DRB1-DQB1 genotypes, we established that these loci would only contribute to a 2-fold increase in T1D prevalence in MS patients. From this evidence, we conclude that shared disease associations due to the HLA-DRB1-DQB1 loci provide only a partial explanation for the observed increased prevalence of T1D in Sardinian MS patients. The data suggest that variation at other non-HLA class II loci, and/or unknown environmental factors contribute significantly to the co-occurrence of these two traits.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{motzo_heterogeneity_2004,

title = {Heterogeneity in the magnitude of the insulin gene effect on HLA risk in type 1 diabetes.},

author = {Motzo, Costantino and Contu, Daniela and Cordell, Heather J. and Lampis, Rosanna and Congia, Mauro and Marrosu, Maria Giovanna and Todd, John A. and Devoto, Marcella and Cucca, Francesco},

issn = {0012-1797 0012-1797},

year  = {2004},

date = {2004-12-01},

journal = {Diabetes},

volume = {53},

number = {12},

pages = {3286--3291},

abstract = {There is still uncertainty concerning the joint action of the two established type 1 diabetes susceptibility loci, the HLA class II DQB1 and DRB1 genes (IDDM1) and the insulin gene (INS) promoter (IDDM2). Some previous studies reported independence, whereas others suggested heterogeneity in the relative effects of the genotypes at these disease loci. In this study, we have assessed the combined effects of the HLA-DQB1/DRB1 and INS genotypes in 944 type 1 diabetic patients and 1,023 control subjects, all from Sardinia. Genotype variation at INS significantly influenced disease susceptibility in all HLA genotype risk categories. However, there was a significant heterogeneity (P = 2.4 x 10(-4)) in the distribution of the INS genotypes in patients with different HLA genotypes. The INS predisposing genotype was less frequent (74.9%) in high-risk HLA genotype-positive patients than in those with HLA intermediate-risk (86.1%) and low-risk (84.8%) categories. Gene-gene interaction modeling led to rejection of the additive model, whereas a multiplicative model showed a better, albeit still partial, fit to the observed data. These genetic results are consistent with an interaction between the protein products of the HLA and INS alleles, in which both the affinity of the various HLA class II molecules for a preproinsulin-derived peptide and the levels of this peptide in the thymus act jointly as key regulators of type 1 diabetes autoimmunity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid15564141,

title = {IL-3 or IL-7 increases ex vivo gene transfer efficiency in AĐA-SCIĐ BM CĐ34+ cells while maintaining in vivo lymphoid potential},

author = {F Ficara and D B Superchi and R J Hernández and C Mocchetti and N Carballido-Perrig and G Andolfi and S Deola and A Colombo and C Bordignon and J M Carballido and M G Roncarolo and A Aiuti},

year  = {2004},

date = {2004-12-01},

journal = {Mol Ther},

volume = {10},

number = {6},

pages = {1096--1108},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid15300850,

title = {ŦCIRG1-dependent recessive osteopetrosis: mutation analysis, functional identification of the splicing defects, and in vitro rescue by U1 snRNA},

author = {L Susani and A Pangrazio and C Sobacchi and A Taranta and G Mortier and R Savarirayan and A Villa and P Orchard and P Vezzoni and A Albertini and A Frattini and F Pagani},

year  = {2004},

date = {2004-09-01},

journal = {Hum Mutat},

volume = {24},

number = {3},

pages = {225--235},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{koeleman_genotype_2004,

title = {Genotype effects and epistasis in type 1 diabetes and HLA-DQ trans dimer associations with disease.},

author = {Koeleman, B. P. C. and Lie, B. A. and Undlien, D. E. and Dudbridge, F. and Thorsby, E. and de Vries, R. R. P. and Cucca, F. and Roep, B. O. and Giphart, M. J. and Todd, J. A.},

doi = {10.1038/sj.gene.6364106},

issn = {1466-4879 1466-4879},

year  = {2004},

date = {2004-08-01},

journal = {Genes Immun},

volume = {5},

number = {5},

pages = {381--388},

abstract = {Alleles of HLA class II genes DQB1, DQA1, and DRB1 in the MHC region are major determinants of genetic predisposition to type 1 diabetes (T1D). Several alleles of each of these three loci are associated with susceptibility or protection from disease. In addition, relative risks for some DR-DQ genotypes are not simply the sum or product of the single haplotype relative risks. For example, the risk of the DRB1*03-DQB1*02/DRB1*0401-DQB1*0302 genotype is often found to be higher than for the individual DRB1*03-DQB1*02 and DRB1*0401-DQB1*0302 homozygous genotypes. It has been hypothesized that this synergy or epistasis occurs through formation of highly susceptible trans-encoded HLA-DQ(alpha 1, beta 1) heterodimers. Here, we evaluated this hypothesis by estimating the disease associations of the range of DR-DQ genotypes and their inferred dimers in a large collection of nuclear families. We determined whether the risk of haplotypes in DRB1*0401-DQB1*0302-positive genotypes relative to the DRB1*03-DQB1*02-positive genotypes is different from that of DRB1*01-DQB1*0501, which we used as a baseline reference. Several haplotypes showed a different risk compared to DRB1*01-DQB1*0501, which correlated with their ability to form certain trans-encoded DQ dimers. This result provides new evidence for the potential importance of trans-encoded HLA DQ molecules in the determination of},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{zavattari_no_2004,

title = {No association between variation of the FOXP3 gene and common type 1 diabetes in the Sardinian population.},

author = {Zavattari, Patrizia and Deidda, Elisabetta and Pitzalis, Maristella and Zoa, Barbara and Moi, Loredana and Lampis, Rosanna and Contu, Daniela and Motzo, Costantino and Frongia, Paola and Angius, Efisio and Maioli, Mario and Todd, John A. and Cucca, Francesco},

issn = {0012-1797 0012-1797},

year  = {2004},

date = {2004-07-01},

journal = {Diabetes},

volume = {53},

number = {7},

pages = {1911--1914},

abstract = {Mutations of the forkhead/winged helix transcription factor FOXP3 gene on chromosome Xp11.23 cause a rare recessive monogenic disorder called IPEX (immune dysregulation, polyendocrinopathy, including type 1 diabetes, enteropathy, and},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid15056605,

title = {Foxl2 disruption causes mouse ovarian failure by pervasive blockage of follicle development},

year  = {2004},

date = {2004-06-01},

journal = {Hum Mol Genet},

volume = {13},

number = {11},

pages = {1171--1181},

abstract = {FOXL2 mutations cause gonadal dysgenesis or premature ovarian failure (POF) in women, as well as eyelid/forehead dysmorphology in both sexes (the 'blepharophimosis-ptosis-epicanthus inversus syndrome', BPES). Here we report that mice lacking Foxl2 recapitulate relevant features of human BPES: males and females are small and show distinctive craniofacial morphology with upper eyelids absent. Furthermore, in mice as in humans, sterility is confined to females. Features of Foxl2 null animals point toward a new mechanism of POF, with all major somatic cell lineages failing to develop around growing oocytes from the time of primordial follicle formation. Foxl2 disruption thus provides a model for histogenesis and reproductive competence of the ovary.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid15384985,

title = {The distal beta-globin CACCC box is required for maximal stimulation of the beta-globin gene by EKLF},

author = { M. G. Marini and I. Asunis and L. Porcu and M. G. Salgo and M. G. Loi and A. Brucchietti and A. Cao and P. Moi},

year  = {2004},

date = {2004-01-01},

journal = {Br J Haematol},

volume = {127},

number = {1},

pages = {114--117},

abstract = {The transcription factor erythroid Kruppel-like factor (EKLF) specifically activates the beta-globin gene by interacting with the proximal beta-globin CACCC box, a known hot spot for thalassaemia mutations. This study investigated whether EKLF could also bind to, and activate from, the distal CACCC, which is a rare site of thalassaemia mutations. Using band shift and transient expression analysis with wild type, single and double CACCC mutants, we established that the distal CACCC box is weakly bound by EKLF, but, when mutated, significantly impairs EKLF-dependent beta-globin stimulation. Thus, EKLF requires both CACCC boxes to maximally stimulate the beta-globin gene.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{maier_testing_2003,

title = {Testing the possible negative association of type 1 diabetes and atopic disease by analysis of the interleukin 4 receptor gene.},

author = {Maier, L. M. and Twells, R. C. J. and Howson, J. M. M. and Lam, A. C. and Clayton, D. G. and Smyth, D. J. and Savage, D. and Carson, D. and Patterson, C. C. and Smink, L. J. and Walker, N. M. and Burren, O. S. and Nutland, S. and Rance, H. and Tuomilehto-Wolf, E. and Tuomilehto, J. and Guja, C. and Ionescu-Tirgoviste, C. and Undlien, D. E. and Ronningen, K. S. and Cucca, F. and Todd, J. A.},

doi = {10.1038/sj.gene.6364007},

issn = {1466-4879 1466-4879},

year  = {2003},

date = {2003-10-01},

journal = {Genes Immun},

volume = {4},

number = {7},

pages = {469--475},

abstract = {Variations in the interleukin 4 receptor A (IL4RA) gene have been reported to be associated with atopy, asthma, and allergy, which may occur less frequently in subjects with type 1 diabetes (T1D). Since atopy shows a humoral immune reactivity pattern, and T1D results from a cellular (T lymphocyte) response, we hypothesised that alleles predisposing to atopy could be protective for T1D and transmitted less often than the expected 50% from heterozygous parents to offspring with T1D. We genotyped seven exonic single nucleotide polymorphisms (SNPs) and the -3223 CtextgreaterT SNP in the putative promoter region of IL4RA in up to 3475 T1D families, including 1244 Finnish T1D families. Only the -3223 CtextgreaterT SNP showed evidence of negative association (P=0.014). There was some evidence for an interaction between -3233 CtextgreaterT and the T1D locus IDDM2 in the insulin gene region (P=0.001 in the combined and P=0.02 in the Finnish data set). We, therefore, cannot rule out a genetic effect of IL4RA in T1D, but it is not a major one.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12826371,

title = {T-cell receptor repertoire in healthy Sardinian subjects},

author = {Bonfigli, S. and Doro, M. G. and Fozza, C. and Derudas, D. and Dore, F. and Longinotti, M.},

year  = {2003},

date = {2003-07-01},

journal = {Hum Immunol},

volume = {64},

number = {7},

pages = {689--695},

abstract = {The T-cell receptor (TCR) Vbeta gene usage of CD4+ and CD8+ T-cell subpopulations was evaluated by flow cytometric analysis and by CDR3 spectratyping in healthy subjects belonging to Sardinian population, which is ethnically homogeneous and genetically distant from all other Italian and Caucasoid groups. As described in healthy Caucasian subjects, we found a nonrandom Vbeta gene usage and in some Vbeta families a significant skewed reactivity toward CD4+ T cells. Moreover, different subjects showed expansions in some Vbeta subfamilies, mainly in the CD8+ T cells. By CDR3 spectratyping analysis we found a significantly higher degree of skewness in the TCR Vbeta repertoire of CD8+ than in that of CD4+ T cells. The similarity found in the TCR Vbeta gene usage between the population examined and other Caucasoid groups suggest that the shape of the TCR repertoire is more influenced by rearrangement processes than ethnic background. However, genetic polymorphisms may condition the expression levels of some Vbetas, determining the variability of the TCR repertoire between different populations. Finally, the profound perturbations evidenced in the CD8+ T cell subpopulation could be related to a different response to the antigenic stimulation between CD8+ and CD4+ T lymphocytes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{cucca_[correlation_2003,

title = {[Correlation between major histocompatibility complex (MHC)-class II and type 1 diabetes].},

author = {Cucca, F. and Contu, D. and Zavattari, P. and Murru, D.},

issn = {0391-1977 0391-1977},

year  = {2003},

date = {2003-06-01},

journal = {Minerva Endocrinol},

volume = {28},

number = {2},

pages = {111--122},

abstract = {The autoimmune disease type 1 diabetes (T1D) results from a T lymphocyte-dependent, selective destruction of the insulin-producing pancreatic beta-cells and subsequent irreversible insulin deficiency. The disease is caused by a combination of genetic and environmental factors. Numerous genetic, structural and biological studies have provided a convincing case that in human T1D and in its murine model, the non obese diabetes (NOD) mouse, the major histocompatibility complex (MHC) class II molecules, HLA-DQB1 and -DRB1 and their murine orthologues, IA and IE, are the major genetic determinants. The two loci act as a complex superlocus, with both haplotype- and genotype-specific effects. In humans the HLA class II molecule-association with the disease is constituted by a two-sided gradient from positively associated-high risk to negatively associated-low risk molecules. Very low risk corresponds to dominant protection from the disease. The protein structure of DQ/IA and DR/IE molecules have been established. Molecular modeling work revealed that there are marked similarities both within, and cross species between T1D protective class II molecules. Likewise, the T1D predisposing molecules show conserved similarities that differ with the shared structural patterns observed between the protective molecules. The available data provide evidence for a joint action of the class II peptide-binding pockets P1, P4 and P9 in disease susceptibility and resistance with a main role for P9 in DQ/IA and for P1 and P4 in DR/IE. Overall these observations suggest shared pathways in human and murine T1D.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12782591,

title = {Inhibition of BUB1 results in genomic instability and anchorage-independent growth of normal human fibroblasts},

author = {A Musio and C Montagna and D Zambroni and E Indino and O Barbieri and L Citti and A Villa and T Ried and P Vezzoni},

year  = {2003},

date = {2003-06-01},

journal = {Cancer Res},

volume = {63},

number = {11},

pages = {2855--2863},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Gianfrancesco2003,

title = {Identification of a Novel Gene and a Common Variant Associated with Uric Acid Nephrolithiasis in a Sardinian Genetic Isolate},

author = {Fernando Gianfrancesco and Teresa Esposito and Maria Neve Ombra and Paola Forabosco and Giuseppe Maninchedda and Mauro Fattorini and Stefania Casula and Simona Vaccargiu and Giuseppina Casu and Francesco Cardia and Ivo Deiana and Paola Melis and Mario Falchi and Mario Pirastu},

doi = {10.1086/375628},

issn = {0002-9297},

year  = {2003},

date = {2003-06-00},

journal = {The American Journal of Human Genetics},

volume = {72},

number = {6},

pages = {1479--1491},

publisher = {Elsevier BV},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{ueda_association_2003,

title = {Association of the Ŧ-cell regulatory gene CTLA4 with susceptibility to autoimmune disease.},

author = {Ueda, Hironori and Howson, Joanna M. M. and Esposito, Laura and Heward, Joanne and Snook, Hywel and Chamberlain, Giselle and Rainbow, Daniel B. and Hunter, Kara M. D. and Smith, Annabel N. and Di Genova, Gianfranco and Herr, Mathias H. and Dahlman, Ingrid and Payne, Felicity and Smyth, Deborah and Lowe, Christopher and Twells, Rebecca C. J. and Howlett, Sarah and Healy, Barry and Nutland, Sarah and Rance, Helen E. and Everett, Vin and Smink, Luc J. and Lam, Alex C. and Cordell, Heather J. and Walker, Neil M. and Bordin, Cristina and Hulme, John and Motzo, Costantino and Cucca, Francesco and Hess, J. Fred and Metzker, Michael L. and Rogers, Jane and Gregory, Simon and Allahabadia, Amit and Nithiyananthan, Ratnasingam and Tuomilehto-Wolf, Eva and Tuomilehto, Jaakko and Bingley, Polly and Gillespie, Kathleen M. and Undlien, Dag E. and Ronningen, Kjersti S. and Guja, Cristian and Ionescu-Tirgoviste, Constantin and Savage, David A. and Maxwell, A. Peter and Carson, Dennis J. and Patterson, Chris C. and Franklyn, Jayne A. and Clayton, David G. and Peterson, Laurence B. and Wicker, Linda S. and Todd, John A. and Gough, Stephen C. L.},

doi = {10.1038/nature01621},

issn = {0028-0836 0028-0836},

year  = {2003},

date = {2003-05-01},

journal = {Nature},

volume = {423},

number = {6939},

pages = {506--511},

abstract = {Genes and mechanisms involved in common complex diseases, such as the autoimmune disorders that affect approximately 5% of the population, remain obscure. Here we identify polymorphisms of the cytotoxic T lymphocyte antigen 4 gene (CTLA4)--which encodes a vital negative regulatory molecule of the immune system--as candidates for primary determinants of risk of the common autoimmune disorders Graves' disease, autoimmune hypothyroidism and type 1 diabetes. In humans, disease susceptibility was mapped to a non-coding 6.1 kb 3' region of CTLA4, the common allelic variation of which was correlated with lower messenger RNA levels of the soluble alternative splice form of CTLA4. In the mouse model of type 1 diabetes, susceptibility was also associated with variation in CTLA-4 gene splicing with reduced production of a splice form encoding a molecule lacking the CD80/CD86 ligand-binding domain. Genetic mapping of variants conferring a small disease risk can identify pathways in complex disorders, as exemplified by our discovery of inherited, quantitative alterations of CTLA4 contributing to autoimmune tissue destruction.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid14584882,

title = {Chloride channel ClCN7 mutations are responsible for severe recessive, dominant, and intermediate osteopetrosis},

author = {A Frattini and A Pangrazio and L Susani and C Sobacchi and M Mirolo and M Abinun and M Andolina and A Flanagan and E M Horwitz and E Mihci and L D Notarangelo and U Ramenghi and A Teti and J Van Hove and D Vujic and T Young and A Albertini and P J Orchard and P Vezzoni and A Villa},

year  = {2003},

date = {2003-01-01},

journal = {J Bone Miner Res},

volume = {18},

number = {10},

pages = {1740--1747},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{contu_sex-related_2002,

title = {Sex-related bias and exclusion mapping of the nonrecombinant portion of chromosome Y in human type 1 diabetes in the isolated founder population of Sardinia.},

author = {Contu, Daniela and Morelli, Laura and Zavattari, Patrizia and Lampis, Rosanna and Angius, Efisio and Frongia, Paola and Murru, Daniela and Maioli, Mario and Francalacci, Paolo and Todd, John A. and Cucca, Francesco},

issn = {0012-1797 0012-1797},

year  = {2002},

date = {2002-12-01},

journal = {Diabetes},

volume = {51},

number = {12},

pages = {3573--3576},

abstract = {A male excess in Sardinian type 1 diabetic cases has previously been reported and was largely restricted to those patients carrying the HLA-DR3/nonDR4 genotype. In the present study, we have measured the male- to-female (M:F) ratio in a sample set of 542 newly collected, early-onset type 1 diabetic Sardinian patients. This data not only confirm the excess of male type 1 diabetic patients overall (M:F ratio = 1.3},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12150951,

title = {Evidence for a role of the nerve growth factor receptor ŦrĄ in tyrosine phosphorylation and processing of beta-APP},

author = {P E Tarr and C Contursi and R Roncarati and C Noviello and E Ghersi and M H Scheinfeld and N Zambrano and T Russo and L DÁdamio},

year  = {2002},

date = {2002-07-01},

journal = {Biochem Biophys Res Commun},

volume = {295},

number = {2},

pages = {324--329},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12089448,

title = {Correction of AĐA-SCIĐ by stem cell gene therapy combined with nonmyeloablative conditioning},

year  = {2002},

date = {2002-06-01},

journal = {Science},

volume = {296},

number = {5577},

pages = {2410--2413},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12089448b,

title = {Correction of AĐA-SCIĐ by stem cell gene therapy combined with nonmyeloablative conditioning},

year  = {2002},

date = {2002-06-01},

journal = {Science},

volume = {296},

number = {5577},

pages = {2410--2413},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12089448c,

title = {Correction of AĐA-SCIĐ by stem cell gene therapy combined with nonmyeloablative conditioning},

year  = {2002},

date = {2002-06-01},

journal = {Science},

volume = {296},

number = {5577},

pages = {2410--2413},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12077301,

title = {Đome formation in cell cultures as expression of an early stage of lactogenic differentiation of the mammary gland},

author = {I Zucchi and L Bini and D Albani and R Valaperta and S Liberatori and R Raggiaschi and C Montagna and L Susani and O Barbieri and V Pallini and P Vezzoni and R Dulbecco},

year  = {2002},

date = {2002-06-01},

journal = {Proc Natl Acad Sci U S A},

volume = {99},

number = {13},

pages = {8660--8665},

keywords = {},

pubstate = {published},

tppubtype = {article}

}