title: 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.
authors.affiliation: UMR 5533 CNRS, Hôpital Cardiologique, Pessac, France.
authors.forename: J
authors.initials: J
authors.lastname: Ruan
authors.forename: O
authors.initials: O
authors.lastname: Peyruchaud
authors.forename: L
authors.initials: L
authors.lastname: Alberio
authors.forename: G
authors.initials: G
authors.lastname: Valles
authors.forename: K
authors.initials: K
authors.lastname: Clemetson
authors.forename: F
authors.initials: F
authors.lastname: Bourre
authors.forename: A T
authors.initials: AT
authors.lastname: Nurden
mesh_terms: D015153:Blotting, Western; D002675:Child, Preschool; D005091:Exons; D006579:Heterozygote; D006801:Humans; D008297:Male; D010375:Pedigree; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D017422:Sequence Analysis, DNA; D013915:Thrombasthenia / Q000235:genetics*
chemical_list: D019039:Platelet Glycoprotein GPIIb-IIIa Complex