Double heterozygosity of the GPIIb gene in a Swiss patient with Glanzmann's thrombasthenia.

Abstract:

:Glanzmann's thrombasthenia (GT) results from a qualitative or quantitative defect of GPIIb-IIIa complexes (integrin alphaIIbbeta3). the fibrinogen receptor on platelets. This integrin plays a critical role in platelet aggregation. In this report we describe the molecular abnormalities of a patient with clinical and laboratory findings typical of type I Glanzmann's thrombasthenia. SDS-PAGE with Western blotting revealed an absence of GPIIb but small amounts of normally migrating GPIIIa in his platelets. A non-radioactive PCR-SSCP procedure and direct sequence analysis of PCR-amplified DNA fragments showed the patient to be a compound heterozygote for mutations in the GPIIb gene. A single point mutation (G to A) at nucleotide 1064 of the cDNA derived from the mother's allele led to a Glu324 to Lys amino acid substitution in GPIIb. It was responsible for a MscI restriction site in exon 12 of the GPIIb gene. This amino acid substitution changes the electric charge between the second and third Ca++-binding domains of GPIIb. The second mutation was inherited from his father and is in exon 18 of the GPIIb gene. It was a T --> C base transition at position 1787 of GPIIb cDNA and results in a Ile565 to Thr substitution. The two GPIIb mutations identified in this study will provide new information on GPIIb-IIIa structure and biosynthesis.

journal_name

Br J Haematol

authors

Ruan J,Peyruchaud O,Alberio L,Valles G,Clemetson K,Bourre F,Nurden AT

doi

10.1046/j.1365-2141.1998.00852.x

subject

Has Abstract

pub_date

1998-09-01 00:00:00

pages

918-25

issue

4

eissn

0007-1048

issn

1365-2141

journal_volume

102

pub_type

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