title: A new variant of Bernard-Soulier syndrome characterized by dysfunctional glycoprotein (GP) Ib and severely reduced amounts of GPIX and GPV.
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, GPIbalpha 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 GPIbalpha 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 GPIbalpha, 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.
authors.affiliation: Internal Medicine and Medical Oncology, University of Pavia, IRCCS San Matteo, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Noris
authors.forename: E
authors.initials: E
authors.lastname: Arbustini
authors.forename: P
authors.initials: P
authors.lastname: Spedini
authors.forename: S
authors.initials: S
authors.lastname: Belletti
authors.forename: C L
authors.initials: CL
authors.lastname: Balduini
mesh_terms: D019943:Amino Acid Substitution; D001606:Bernard-Soulier Syndrome / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D001760:Bleeding Time; D004247:DNA / Q000032:analysis; D003894:Deamino Arginine Vasopressin / Q000627:therapeutic use; D005260:Female; D006490:Hemostatics / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000235:genetics* / Q000378:metabolism
chemical_list: D006490:Hemostatics; D019038:Platelet Glycoprotein GPIb-IX Complex; D004247:DNA; D003894:Deamino Arginine Vasopressin