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Molecular characterization of two mutations in platelet glycoprotein (GP) Ibα in two Finnish Bernard–Soulier syndrome families
Author(s) -
Koskela S.,
Partanen J.,
Salmi T. T.,
Kekomäki R.
Publication year - 1999
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.1999.tb01739.x
Subject(s) - bernard–soulier syndrome , compound heterozygosity , glycoprotein ib , point mutation , platelet glycoprotein gpib ix complex , mutation , platelet membrane glycoprotein , platelet , microbiology and biotechnology , ristocetin , genetics , von willebrand disease , von willebrand factor , medicine , gene , biology , glycoprotein
Bernard‐Soulier syndrome (BSS) is a rare hereditary bleeding disorder and macrothrombocytopenia which is caused by a defect in the platelet glycoprotein Ib/IX/V (GP Ib/IX/V) complex, the receptor for von Willebrand factor and thrombin. Here we report the molecular basis of the classical form of BSS in two unrelated Finnish patients, both with a life‐long history of severe bleeding. Flow cytometry and immunoblotting showed no expression of GP Ib/IX, GP Ibα, GP Ibβ or GP IX (less than 10%) in the patients' platelets. No expression of GP V (<10%) was observed in propositus 1, but a residual amount was found in propositus 2 (24%). DNA sequencing analysis revealed that propositus 1 was compound heterozygous for a two‐base‐pair deletion at Tyr505(T AT ) and a point mutation Leul29(CTC)Pro(CCC) in the GP Ibα gene. Propositus 2 was homozygous for the Tyr505(T AT ) deletion. The nine relatives who were heterozygous for either of the mutations also had low levels of GP Ibα (74–90%). Hence, Bernard‐Soulier patients homozygous or compound heterozygous for Tyr505(T AT ) are severely affected. Interestingly, both mutations have independently been found in three other families in previous reports, suggesting their ancient age or mutational ‘hot spot’.