TY - JOUR
T1 - A new variant of Bernard-Soulier syndrome characterized by dysfunctional glycoprotein (GP) Ib and severely reduced amounts of GPIX and GPV
AU - Noris, Patrizia
AU - Arbustini, Eloisa
AU - Spedini, Pierangelo
AU - Belletti, Simona
AU - Balduini, Carlo Luigi
PY - 1998
Y1 - 1998
N2 - 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 alelle. 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 yon Willebrand factor plasma concentration did not seem to be directly related.
AB - 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 alelle. 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 yon Willebrand factor plasma concentration did not seem to be directly related.
KW - Bernard-Soulier syndrome
KW - DDAVP
KW - Platelet glycoproteins
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U2 - 10.1046/j.1365-2141.1998.01100.x
DO - 10.1046/j.1365-2141.1998.01100.x
M3 - Article
C2 - 9886312
AN - SCOPUS:0032424417
VL - 103
SP - 1004
EP - 1013
JO - British Journal of Haematology
JF - British Journal of Haematology
SN - 0007-1048
IS - 4
ER -