Autosomal dominant macrothrombocytopenia in Italy is most frequently a type of heterozygous Bernard-Soulier syndrome

Anna Savoia, Carlo L. Balduini, Maria Savino, Patrizia Noris, Maria Del Vecchio, Silverio Perrotta, Simona Belletti, Vincenzo Poggi, Achille Iolascon

Research output: Contribution to journalArticlepeer-review

Abstract

A form of autosomal dominant macrothrombocytopenia is characterized by mild or no clinical symptoms, normal platelet function, and normal megakaryocyte count. Because this condition has so far received little attention, patients are subject to misdiagnosis and inappropriate therapy. To identify the molecular basis of this disease, 12 Italian families were studied by linkage analysis and mutation screening. Flow cytometry evaluations of platelet membrane glycoproteins (GPs) were also performed. Linkage analysis in 2 large families localized the gene to chromosome 17p, in an interval containing an excellent candidate, the GPIbα gene. GPIbα, together with other proteins, constitutes the plasma von Willebrand factor (vWF) receptor, which is altered in Bernard-Soulier syndrome (BSS). In 6 of 12 families, a heterozygous Ala156Val missense substitution was identified. Platelet membrane GP studies were performed in 10 patients. Eight were distinguished by a reduction of GPs comparable to that found in a BSS heterozygous condition, whereas the other 2, without the Ala156Val mutation, had a normal content of platelet GPs. In conclusion, the current study provides evidence that most (10 of 12) patients with an original diagnosis of autosomal dominant macrothrombocytopenia shared clinical and molecular features with the heterozygous BSS phenotype. The remaining 2 affected subjects represented patients with "true" autosomal dominant macrothrombocytopenia; the GPIb/IX/V complex was normally distributed on the surface of their platelets. Thus, the diagnosis of heterozygous BSS must always be suspected in patients with inherited thrombocytopenia and platelet macrocytosis.

Original languageEnglish
Pages (from-to)1330-1335
Number of pages6
JournalBlood
Volume97
Issue number5
DOIs
Publication statusPublished - Mar 1 2001

ASJC Scopus subject areas

  • Hematology

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