TY - JOUR T1 - Clinical and laboratory features of 103 patients from 42 Italian families with inherited thrombocytopenia derived from the monoallelic Ala156Val mutation of GPIbα (Bolzano mutation). JF - Haematologica Y1 - 2012 A1 - Noris, Patrizia A1 - Perrotta, Silverio A1 - Bottega, Roberta A1 - Pecci, Alessandro A1 - Melazzini, Federica A1 - Civaschi, Elisa A1 - Russo, Sabina A1 - Magrin, Silvana A1 - Loffredo, Giuseppe A1 - Di Salvo, Veronica A1 - Russo, Giovanna A1 - Casale, Maddalena A1 - De Rocco, Daniela A1 - Grignani, Claudio A1 - Cattaneo, Marco A1 - Baronci, Carlo A1 - Dragani, Alfredo A1 - Albano, Veronica A1 - Jankovic, Momcilo A1 - Scianguetta, Saverio A1 - Savoia, Anna A1 - Balduini, Carlo L KW - Adolescent KW - Adult KW - Aged KW - Aged, 80 and over KW - Bernard-Soulier Syndrome KW - Child KW - Child, Preschool KW - Family Health KW - Female KW - Heterozygote KW - Humans KW - Infant KW - Italy KW - Male KW - Membrane Glycoproteins KW - Middle Aged KW - Mutation, Missense KW - Platelet Aggregation KW - Platelet Count KW - Platelet Glycoprotein GPIb-IX Complex KW - Polymorphism, Genetic KW - Thrombocytopenia KW - Thrombopoietin KW - Tubulin KW - Young Adult AB -

BACKGROUND: Bernard-Soulier syndrome is a very rare form of inherited thrombocytopenia that derives from mutations in GPIbα, GPIbβ, or GPIX and is typically inherited as a recessive disease. However, some years ago it was 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: Over the past 10 years, we have searched for the Bolzano mutation in all subjects referred to our institutions because of 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 expression was variable, patients with this mutation typically had a mild form of Bernard-Soulier syndrome with mild thrombocytopenia and bleeding tendency. The most indicative laboratory findings were enlarged platelets and reduced GPIb/IX/V platelet expression; 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.

VL - 97 IS - 1 U1 - http://www.ncbi.nlm.nih.gov/pubmed/21933849?dopt=Abstract ER -