Three novel integrin β3 subunit missense mutations (H280P, C560F, and G579S) in thrombasthenia, including one (H280P) prevalent in Japanese patients

被引:41
作者
Ambo, H
Kamata, T
Handa, M
Taki, M
Kuwajima, M
Kawai, Y
Oda, A
Murata, M
Takada, Y
Watanabe, K
Ikeda, Y
机构
[1] Keio Univ, Sch Med, Ctr Blood, Shinjuku Ku, Tokyo 1608582, Japan
[2] Keio Univ, Sch Med, Dept Internal Med, Shinjuku Ku, Tokyo 1608582, Japan
[3] Keio Univ, Sch Med, Lab Med, Shinjuku Ku, Tokyo 1608582, Japan
[4] Scripps Res Inst, Dept Vasc Biol, La Jolla, CA 92037 USA
[5] St Marianna Univ, Sch Med, Dept Pediat, Kanagawa 2168511, Japan
[6] Kagawa Prefectural Cent Hosp, Dept Clin Pathol, Kagawa 7608557, Japan
关键词
D O I
10.1006/bbrc.1998.9526
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 beta 3 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 alpha IIb beta 3 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. (C) 1998 Academic Press.
引用
收藏
页码:763 / 768
页数:6
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