A new variant of Bernard‐Soulier syndrome characterized by dysfunctional glycoprotein (GP) Ib and severely reduced amounts of GPIX and GPV

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Abstract
We describe a new variant of Bernard‐Soulier syndrome characterized by almost normal amounts of GPIb and severely reduced GPIX and GPV. Despite surface expression, GPIbα failed to support ristocetin‐induced platelet agglutination and to bind two conformation‐dependent monoclonal antibodies, suggesting a qualitative defect. Sequence analysis of the gene coding for GPIX revealed a T‐to‐C substitution at base 1811, leading to a Leu40Pro conversion, whereas no defects were found in the coding region of the GPIbα gene. Allele‐specific restriction enzyme analysis showed that the propositus and one of his sisters, both with severe bleeding diathesis, were homozygous for the GPIX mutation; the members of the family with mild bleeding diathesis and/or giant platelets in the peripheral blood were heterozygous, whereas the healthy ones were homozygous for the normal allele. Infusion of 1‐desamino‐8‐ d‐arginine vasopressin normalized bleeding time in the two severely affected patients, although it did not modify ristocetin‐induced platelet agglutination or membrane expression of GPIbα, GPIX, GPIIb–IIIa and GMP‐140. Moreover, in one patient, normalization of bleeding time and rise of von Willebrand factor plasma concentration did not seem to be directly related.

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