p.Pro27Ser is rare in the SardiNIA population cohort (frequency of 0.45%) and not reported elsewhere. GP1BB is involved in Bernard-Soulier syndrome (BSS), a rare autosomal recessive bleeding disorder caused by a defect in the platelet GPIb-IX-V protein complex. Consistently, the 57 identified heterozygous individuals showed mild thrombocytopenia and morphologically enlarged platelets. Our molecular modeling analyses suggested a reduction in the stability of the p.Pro27Ser GPIb-beta protein, that explain a corresponding reduction of the expression of two GPIb-IX-V-complex components, GPIb-alpha and GPIX, as functional flow-cytometry experiments indicated. These observations predict that in homozygosity, as well as in individuals carrying specific compound heterozygous configurations, this variant likely causes BSS.
Full text link: https://onlinelibrary.wiley.com/doi/full/10.1111/bjh.17090