Highly prevalent SERPINB7 founder mutation causes pseudodominant inheritance pattern in Nagashima-type palmoplantar keratosis
Highly prevalent SERPINB7 founder mutation causes pseudodominant inheritance pattern in Nagashima-type palmoplantar keratosis
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DOI：
10.1111/bjd.13076
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发表时间：
2014-10-01
影响因子：
10.3
通讯作者：
Shimizu, H.
中科院分区：
文献类型：
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作者：
Mizuno, O.;Nomura, T.;Shimizu, H.
研究背景：nagashima型掌跖角化病（NPPK）是一种以弥漫性侵润性掌跖角化病（PPK）为特征的常染色体隐性遗传病。最近，SERPINB7（编码丝氨酸蛋白酶抑制剂超家族成员并在表皮中大量表达）假定的功能丧失突变已被确定为NPPK的原因。目的进一步证实SERPINB7突变在NPPK发病机制中的作用。方法采用Sanger和/或全外显子组测序对10个日本NPPK家族进行分析。结果我们在SERPINB7中发现了一个新的零突变和三个复发的零突变。在所有家族中，NPPK性状均以常染色体隐性遗传方式遗传；其中一个家族存在NPPK未见的假显性遗传。结论这些数据清楚地提供了进一步的证据，证明NPPK是由SERPINB7的功能缺失突变引起的。
BackgroundNagashima-type palmoplantar keratosis (NPPK) is a distinct autosomal recessive genodermatosis characterized by diffuse transgressive palmoplantar keratoderma (PPK). Very recently, putative loss-of-function mutations in SERPINB7, which encodes a member of the serine protease inhibitor superfamily and is abundantly expressed in the epidermis, have been identified as a cause of NPPK.ObjectivesTo confirm further the role of SERPINB7 mutations in the pathogenesis of NPPK.MethodsWe analysed 10 Japanese families with NPPK using Sanger and/or whole-exome sequencing.ResultsWe identified one novel and three recurrent null mutations in SERPINB7. In all the families, the NPPK trait was inherited in an autosomal recessive manner; in one of the families, there was pseudodominant inheritance, which had not been described in NPPK.ConclusionsThese data clearly provide further evidence that NPPK is caused by loss-of-function mutations in SERPINB7.