错义突变
遗传学
外显子
生物
内含子
蛋白质S
蛋白质C
蛋白质S缺乏症
蛋白质C缺乏
基因
点突变
突变
终止密码子
分子生物学
表型
编码区
先证者
静脉血栓形成
医学
内科学
血栓形成
生物化学
作者
RE Simmonds,H Ireland,G Kunz,Da Lane
出处
期刊:Blood
[American Society of Hematology]
日期:1996-12-01
卷期号:88 (11): 4195-4204
被引量:33
标识
DOI:10.1182/blood.v88.11.4195.bloodjournal88114195
摘要
Protein S is a protein C-dependent and independent inhibitor of the coagulation cascade. Deficiency of protein S is an established risk factor for venous thromboembolism. We have used a strategy of specific amplification of the coding regions and intron/exon boundaries of the active protein S gene (PROS1) and direct single-strand solid phase sequencing, to seek mutations in 35 individuals with phenotypic protein S deficiency. Nineteen point mutations (16 novel) in 19 probands (or relatives of probands) with venous thromboembolism are reported here. Fifteen of the 19 mutations were expected to be causal and included 10 missense mutations (Lys9Glu, Glu26Ala, Gly54Glu, Cys145Tyr, Cys200Ser, Ser283Pro, Gly340Asp, Cys408Ser, Ser460Pro, and Cys625Arg). Three of the 15 mutations resulted in premature stop codons (delete T 635 producing a stop codon at position 126, Lys368stop and Tyr595stop) and two were at intron/exon boundaries (+1 G to A in intron d and +3 A to C in intron j). Of the remaining four mutations, three were within intronic sequence and one was a silent mutation within the coding region and did not alter amino acid composition. In two of the 10 missense mutations, reduced plasma protein S activity compared with antigen level suggested the presence of variant (type II) protein S.
科研通智能强力驱动
Strongly Powered by AbleSci AI