Clinical and laboratory features of 103 patients from 42 Italian families with inherited thrombocytopenia derived from the monoallelic Ala156Val mutation of GPIb{alpha} (Bolzano mutation).

Background. Bernard-Soulier syndrome is a very rare form of inherited thrombocytopenia that derives from mutations in GPIb alpha, GPIb beta, or GPIX and is typically inherited as a recessive disease. However, some years ago it has been shown that the monoallelic c.515C>T transition in the GPIBA gene (Bolzano mutation) was responsible for macrothrombocytopenia in a few Italian patients. Design and Methods. In the past 10 years, we have searched for Bolzano mutation in all subjects referred to our institutions for an autosomal, dominant form of thrombocytopenia of unknown origin. Results. We identified 42 new Italian families (103 cases) with a thrombocytopenia induced by monoallelic Bolzano mutation. Analyses of the geographic origin of affected pedigrees and haplotypes indicated that this mutation originated in southern Italy. Although the clinical expressivity was variable, patients with this mutation typically had a mild form of Bernard-Soulier syndrome with a mild thrombocytopenia and bleeding tendency. The most indicative laboratory findings were an enlarged platelet size and reduced GPIb/IX/V platelet expression, although in vitro platelet aggregation was normal in nearly all of the cases. Conclusions. Our study indicates that monoallelic Bolzano mutation is the most frequent cause of inherited thrombocytopenia in Italy, affecting 20% of patients recruited at our institutions during the last 10 years. Because many people from southern Italy have emigrated during the last century, this mutation may have spread to other countries.