Genetic analysis of protein C deficiency in nineteen Japanese families: Five recurrent defects can explain half of the deficiencies
Genetic analysis of protein C deficiency in nineteen Japanese families: Five recurrent defects can explain half of the deficiencies
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DOI：
10.1016/s0049-3848(98)00131-5
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发表时间：
1998-11-15
影响因子：
7.5
通讯作者：
Kato, H
中科院分区：
文献类型：
--
作者：
Miyata, T;Sakata, T;Kato, H
我们一直在研究蛋白C缺乏症的分子基础。在这项研究中，我们确定了19个日本家庭的蛋白C缺乏症的分子缺陷，使用聚合酶链反应（PCR）和单链构象多态性（SSCP）分析相结合的策略。我们发现了10个错义突变，1个框内缺失，1个移码缺失，1个移码添加和1个剪接位点突变，其中5个是新的。从67个日本家庭与蛋白C缺乏症的遗传分析结果，在这个和以前的研究中，经常性的缺陷，包括Phe139Val和Met365Ile取代和Lys150缺失，G8857缺失，和剪接位点突变的G3079A只发现在日本的主题，似乎是一个创始人的影响。与此相反，Arg169Trp、Arg286His、Va1297Met和Asp359Asn替换，都发生在CG二核苷酸上，不仅在日本人中，而且在西方人群中也普遍观察到，这表明这些是蛋白C基因突变的热点。共有43个家族发现了这9种复发性分子缺陷，占日本蛋白C缺乏症家族的64%。特别是，Phe139Val，Arg169Trp，Val297Met和Met364Ile替换和G8857缺失的复发性缺陷在33个家庭中被发现，占日本蛋白C缺乏症家庭的49%。为了鉴定日本蛋白C缺乏症患者的遗传缺陷，通过限制性内切酶切割筛选这些复发性缺陷是一种合理的方法。(C)1998 Elsevier Science Ltd.
We have been studying the molecular basis of protein C deficiency. In this study, we determined the molecular defects of protein C deficiency in 19 Japanese families by using a strategy combining polymerase chain reaction (PCR) and single-strand conformational polymorphism (SSCP) analysis. We identified 10 missense mutations, 1 in-frame deletion, 1 frameshift deletion, 1 frameshift addition, and 1 splice site mutation, 5 of which were novel. From the results of genetic analysis of 67 Japanese families with protein C deficiency reported in this and previous studies, the recurrent defects including Phe139Val and Met365Ile substitutions and a Lys150 d letion, a G8857 deletion, and a splice site mutation of G3079A were only found in Japanese subjects and seemed to be a founder effect. In contrast, Arg169Trp, Arg286His, Va1297Met, and Asp359Asn substitutions, all occurring at CG dinucleotides, were commonly observed in not only Japanese but also Western populations, indicating that these are hot spots for mutation in the protein C gene. These 9 recurrent molecular defects were found in 43 families in total, accounting 64% of Japanese families with protein C deficiency. In particular, the recurrent defects of Phe139Val, Arg169Trp, Val297Met, and Met364Ile substitutions and a G8857 deletion were found in 33 families in total, accounting for 49% of Japanese families with protein C deficiency. For the identification of the genetic defect in Japanese patients with protein C deficiency, screening of these recurrent defects by using restriction enzyme cleavage is a rational method. (C) 1998 Elsevier Science Ltd.