title: Three novel integrin beta3 subunit missense mutations (H280P, C560F, and G579S) in thrombasthenia, including one (H280P) prevalent in Japanese patients.
abstract: We analyzed three unrelated Japanese patients with type II Glanzmann thrombasthenia (GT) for associated mutations. Polymerase chain reaction and subsequent direct sequencing of platelet RNA and genomic DNA revealed three single nucleotide substitutions of the integrin beta3 subunit gene (His (CAT)-280 to Pro (CCT), Cys (TGT)-560 to Phe (TTT), and Gly(GGC)-579 to Ser(AGC)). Interestingly, the three unrelated patients all had the H280P mutation; one was homozygous and the other two heterozygous for this mutation. Ectopic expression of wild type and mutant complexes in Chinese hamster ovary cells revealed decreased surface expression of the mutated alphaIIbbeta3 complexes, thus demonstrating that these mutations may result in the mild GT phenotypes. The identification of three unrelated patients having the same mutation (H280P) suggests that this mutation might be prevalent in the Japanese thrombasthenic population.
authors.affiliation: School of Medicine, Keio University, Tokyo, 160-8582, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ambo
authors.forename: T
authors.initials: T
authors.lastname: Kamata
authors.forename: M
authors.initials: M
authors.lastname: Handa
authors.forename: M
authors.initials: M
authors.lastname: Taki
authors.forename: M
authors.initials: M
authors.lastname: Kuwajima
authors.forename: Y
authors.initials: Y
authors.lastname: Kawai
authors.forename: A
authors.initials: A
authors.lastname: Oda
authors.forename: M
authors.initials: M
authors.lastname: Murata
authors.forename: Y
authors.initials: Y
authors.lastname: Takada
authors.forename: K
authors.initials: K
authors.lastname: Watanabe
authors.forename: Y
authors.initials: Y
authors.lastname: Ikeda
mesh_terms: D000368:Aged; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics*; D016466:CHO Cells; D002675:Child, Preschool; D006224:Cricetinae; D005260:Female; D005787:Gene Frequency; D006579:Heterozygote; D006801:Humans; D039661:Integrin beta3; D016023:Integrins / Q000096:biosynthesis / Q000235:genetics*; D007564:Japan; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010980:Platelet Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D015995:Prevalence; D011994:Recombinant Proteins / Q000096:biosynthesis; D017422:Sequence Analysis, DNA; D013915:Thrombasthenia / Q000145:classification / Q000235:genetics*
chemical_list: D015703:Antigens, CD; D039661:Integrin beta3; D016023:Integrins; D010980:Platelet Membrane Glycoproteins; D011994:Recombinant Proteins