Maura Mingoia

@article{Mingoia2025-rn,

title = {A novel intronic variant in the KH3 domain of HNRNPK leads  to a mild form of Au-Kline syndrome},

author = {Maura Mingoia and Alessandra Meloni and Silvia Sedda and Sanaa Choufani and Isadora Asunis and Giorgia Gemma and Antonio Ammendola and Arteen Torabi-Marashi and Eleonora Venere and Gabriella Maria Squeo and Vincenzo Rallo and Maria Giuseppina Marini and Paolo Moi and Salvatore Savasta and Rosanna Weksberg and Giuseppe Merla and Andrea Angius},

year  = {2025},

date = {2025-11-01},

urldate = {2025-11-01},

journal = {Clin. Genet.},

volume = {108},

number = {5},

pages = {576--581},

publisher = {Wiley},

abstract = {Despite the massive adoption of sequencing technologies, 

 disease-specific diagnosis remains challenging, particularly for 

 genes with highly homologous pseudogenes like HNRNPK. Pathogenic 

 HNRNPK variants cause Au-Kline syndrome (AKS), a 

 neurodevelopmental disorder with malformations and distinctive 

 facial features. We validated a novel de novo HNRNPK intronic 

 variant (c.1192-3 C>A, p.Leu398ValfsTer21) in a patient 

 previously misdiagnosed with Kabuki Syndrome (KS). By combining 

 sequencing, in vitro splicing assays, molecular modelling, and 

 protein function analysis, we characterised the molecular 

 defect. A unique DNA methylation (DNAm) signature was recently 

 identified in AKS, with missense variants showing an 

 intermediate DNAm pattern, suggesting an epi-genotype-phenotype 

 correlation linked to milder clinical features. The DNAm 

 signature is a valuable tool for variant interpretation, 

 especially in unclear AKS cases. We demonstrate that two 

 independent approaches-functional characterisation and DNAm 

 evaluation-confirmed a partial loss of HNRNPK function and 

 validated an AKS diagnosis with a mild phenotype. Our findings 

 highlight that a multidisciplinary approach integrating genomic 

 and epigenomic analyses with functional studies and clinical 

 assessment significantly improves rare disease diagnosis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Orru2024-ec,

title = {Implications of disease-modifying therapies for multiple  sclerosis on immune cells and response to COVID-19 vaccination},

author = {Valeria Orrù and Valentina Serra and Michele Marongiu and Sandra Lai and Valeria Lodde and Magdalena Zoledziewska and Maristella Steri and Annalisa Loizedda and Monia Lobina and Maria Grazia Piras and Francesca Virdis and Giuseppe Delogu and Maria Giuseppina Marini and Maura Mingoia and Matteo Floris and Marco Masala and M Paola Castelli and Rafaela Mostallino and Jessica Frau and Lorena Lorefice and Gabriele Farina and Marzia Fronza and Daniele Carmagnini and Elisa Carta and Silvy Pilotto and Paola Chessa and Marcella Devoto and Paolo Castiglia and Paolo Solla and Roberto Ignazio Zarbo and Maria Laura Idda and Maristella Pitzalis and Eleonora Cocco and Edoardo Fiorillo and Francesco Cucca},

year  = {2024},

date = {2024-07-01},

urldate = {2024-07-01},

journal = {Front. Immunol.},

volume = {15},

pages = {1416464},

publisher = {Frontiers Media SA},

abstract = {Introduction: Disease-modifying therapies (DMTs) have been shown 

 to improve disease outcomes in multiple sclerosis (MS) patients. 

 They may also impair the immune response to vaccines, including 

 the SARS-CoV-2 vaccine. However, available data on both the 

 intrinsic immune effects of DMTs and their influence on cellular 

 response to the SARS-CoV-2 vaccine are still incomplete. 

 Methods: Here, we evaluated the immune cell effects of 3 DMTs on 

 the response to mRNA SARS-CoV-2 vaccination by comparing MS 

 patients treated with one specific therapy (fingolimod, dimethyl 

 fumarate, or natalizumab) with both healthy controls and 

 untreated patients. We profiled 23 B-cell traits, 57 T-cell 

 traits, and 10 cytokines, both at basal level and after 

 stimulation with a pool of SARS-CoV-2 spike peptides, in 79 MS 

 patients, treated with DMTs or untreated, and 32 healthy 

 controls. Measurements were made before vaccination and at three 

 time points after immunization. Results and Discussion: MS 

 patients treated with fingolimod showed the strongest immune 

 cell dysregulation characterized by a reduction in all measured 

 lymphocyte cell classes; the patients also had increased immune 

 cell activation at baseline, accompanied by reduced specific 

 immune cell response to the SARS-CoV-2 vaccine. Also, anti-spike 

 specific B cells progressively increased over the three time 

 points after vaccination, even when antibodies measured from the 

 same samples instead showed a decline. Our findings demonstrate 

 that repeated booster vaccinations in MS patients are crucial to 

 overcoming the immune cell impairment caused by DMTs and 

 achieving an immune response to the SARS-CoV-2 vaccine 

 comparable to that of healthy controls.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Simbula2023-rj,

title = {miR-365-3p mediates BCL11A and SOX6 erythroid-specific 

 coregulation: A new player in HbF activation},

author = {Michela Simbula and Maria Francesca Manchinu and Maura Mingoia and Mauro Pala and Isadora Asunis and Cristian Antonio Caria and Lucia Perseu and Manan Shah and Merlin Crossley and Paolo Moi and Maria Serafina Ristaldi},

year  = {2023},

date = {2023-12-01},

journal = {Mol. Ther. Nucleic Acids},

volume = {34},

number = {102025},

pages = {102025},

publisher = {Elsevier BV},

abstract = {Hemoglobin switching is a complex biological process not yet 

 fully elucidated. The mechanism regulating the suppression of 

 fetal hemoglobin (HbF) expression is of particular interest 

 because of the positive impact of HbF on the course of diseases 

 such as $beta$-thalassemia and sickle cell disease, hereditary 

 hemoglobin disorders that affect the health of countless 

 individuals worldwide. Several transcription factors have been 

 implicated in the control of HbF, of which BCL11A has emerged as 

 a major player in HbF silencing. SOX6 has also been implicated 

 in silencing HbF and is critical to the silencing of the mouse 

 embryonic hemoglobins. BCL11A and SOX6 are co-expressed and 

 physically interact in the erythroid compartment during 

 differentiation. In this study, we observe that BCL11A knockout 

 leads to post-transcriptional downregulation of SOX6 through 

 activation of microRNA (miR)-365-3p. Downregulating SOX6 by 

 transient ectopic expression of miR-365-3p or gene editing 

 activates embryonic and fetal $beta$-like globin gene 

 expression in erythroid cells. The synchronized expression of 

 BCL11A and SOX6 is crucial for hemoglobin switching. In this 

 study, we identified a BCL11A/miR-365-3p/SOX6 evolutionarily 

 conserved pathway, providing insights into the regulation of the 

 embryonic and fetal globin genes suggesting new targets for 

 treating $beta$-hemoglobinopathies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Boulad2022-ka,

title = {Lentiviral globin gene therapy with reduced-intensity  conditioning in adults with $beta$-thalassemia: a phase 1 trial},

author = {Farid Boulad and Aurelio Maggio and Xiuyan Wang and Paolo Moi and Santina Acuto and Friederike Kogel and Chayamon Takpradit and Susan Prockop and Jorge Mansilla-Soto and Annalisa Cabriolu and Ashlesha Odak and Jinrong Qu and Keyur Thummar and Fang Du and Lingbo Shen and Simona Raso and Rita Barone and Rosario Di Maggio and Lorella Pitrolo and Antonino Giambona and Maura Mingoia and John K Everett and Pascha Hokama and Aoife M Roche and Vito Adrian Cantu and Hriju Adhikari and Shantan Reddy and Eric Bouhassira and Narla Mohandas and Frederic D Bushman and Isabelle Rivi`ere and Michel Sadelain},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Nat. Med.},

volume = {28},

number = {1},

pages = {63--70},

publisher = {Springer Science and Business Media LLC},

abstract = {$beta$-Thalassemias are inherited anemias that are caused by 

 the absent or insufficient production of the $beta$ chain of 

 hemoglobin. Here we report 6-8-year follow-up of four adult 

 patients with transfusion-dependent $beta$-thalassemia who were 

 infused with autologous CD34+ cells transduced with the 

 TNS9.3.55 lentiviral globin vector after reduced-intensity 

 conditioning (RIC) in a phase 1 clinical trial ( NCT01639690) . 

 Patients were monitored for insertional mutagenesis and the 

 generation of a replication-competent lentivirus (safety and 

 tolerability of the infusion product after RIC-primary endpoint) 

 and engraftment of genetically modified autologous CD34+ cells, 

 expression of the transduced $beta$-globin gene and 

 post-transplant transfusion requirements (efficacy-secondary 

 endpoint). No unexpected safety issues occurred during 

 conditioning and cell product infusion. Hematopoietic gene 

 marking was very stable but low, reducing transfusion 

 requirements in two patients, albeit not achieving transfusion 

 independence. Our findings suggest that non-myeloablative 

 conditioning can achieve durable stem cell engraftment but 

 underscore a minimum CD34+ cell transduction requirement for 

 effective therapy. Moderate clonal expansions were associated 

 with integrations near cancer-related genes, suggestive of 

 non-erythroid activity of globin vectors in stem/progenitor 

 cells. These correlative findings highlight the necessity of 

 cautiously monitoring patients harboring globin vectors.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mingoia2021-hv,

title = {Induction of therapeutic levels of HbF in genome-edited 

 primary $beta$0 39-thalassaemia haematopoietic stem and 

 progenitor cells},

author = {Maura Mingoia and Cristian A Caria and Lin Ye and Isadora Asunis and M Franca Marongiu and Laura Manunza and M Carla Sollaino and Jiaming Wang and Annalisa Cabriolu and Ryo Kurita and Yukio Nakamura and Francesco Cucca and Yuet W Kan and M Giuseppina Marini and Paolo Moi},

year  = {2021},

date = {2021-01-01},

journal = {Br. J. Haematol.},

volume = {192},

number = {2},

pages = {395--404},

publisher = {Wiley},

abstract = {Hereditary persistence of fetal haemoglobin (HPFH) is the major 

 modifier of the clinical severity of $beta$-thalassaemia. The 

 homozygous mutation c.-196 C>T in the A$gamma$-globin (HBG1) 

 promoter, which causes Sardinian $delta$$beta$0 -thalassaemia, 

 is able to completely rescue the $beta$-major thalassaemia 

 phenotype caused by the $beta$0 39-thalassaemia mutation, 

 ensuring high levels of fetal haemoglobin synthesis during 

 adulthood. Here, we describe a CRISPR/Cas9 genome-editing 

 approach, combined with the non-homologous end joining (NHEJ) 

 pathway repair, aimed at reproducing the effects of this 

 naturally occurring HPFH mutation in both HBG promoters. After 

 selecting the most efficient guide RNA in K562 cells, we edited 

 the HBG promoters in human umbilical cord blood-derived 

 erythroid progenitor 2 cells (HUDEP-2) and in haematopoietic 

 stem and progenitor cells (HSPCs) from $beta$0 -thalassaemia 

 patients to assess the therapeutic potential of HbF induction. 

 Our results indicate that small deletions targeting the 

 -196-promoter region restore high levels of fetal haemoglobin 

 (HbF) synthesis in all cell types tested. In pools of HSPCs 

 derived from homozygous $beta$0 39-thalassaemia patients, a 

 20% editing determined a parallel 20% increase of HbF compared 

 to unedited pools. These results suggest that editing the region 

 of HBG promoters around the -196 position has the potential to 

 induce therapeutic levels of HbF in patients with most types of 

 $beta$-thalassaemia irrespective of the $beta$-globin gene 

 (HBB) mutations.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}