Yoshida Kazue, Hayashi Ryota, Fujita Hideki, Kubota Masaya, Kondo Mai, Shimomura Yutaka, Niizeki Hironori
Department of Dermatology, National Center for Child Health and Development, Tokyo, Japan.
Laboratory of Genetic Skin Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
J Dermatol. 2015 Jul;42(7):715-9. doi: 10.1111/1346-8138.12882. Epub 2015 Apr 24.
Cleft lip/palate-ectodermal dysplasia syndrome is a rare, autosomal recessive disorder caused by homozygous loss-of-function mutations of the poliovirus receptor-like 1 (PVRL1) gene encoding nectin-1. Nectin-1 is a cell-cell adhesion molecule that is important for the initial step in the formation of adherens junctions and tight junctions; it is expressed in keratinocytes, neurons, and the developing face and palate. Clinical manifestations comprise a unique facial appearance with cleft lip/palate, ectodermal dysplasia, cutaneous syndactyly of the fingers and/or toes, and in some cases, mental retardation. We present the first report, to our knowledge, of an Asian individual with cleft lip/palate-ectodermal dysplasia syndrome with a novel PVRL1 mutation. A 7-year-old Japanese boy, the first child of a consanguineous marriage, showed hypohidrotic ectodermal dysplasia with sparse, brittle, fine, dry hair and hypodontia, the unique facial appearance with cleft lip/palate, cutaneous syndactyly of the fingers and mild mental retardation. Scanning electron microscopic examination of the hair demonstrated pili torti and pili trianguli et canaliculi. Mutation analysis of exon 2 of PVRL1 revealed a novel homozygous nonsense mutation, c.400C>T (p.Arg134*). His parents were heterozygous for the mutant alleles. All four PVRL1 mutations identified in cleft lip/palate-ectodermal dysplasia syndrome to date, including this study, resulted in truncated proteins that lack the transmembrane domain and intracellular domain of nectin-1, which is necessary to initiate the cell-cell adhesion process.
唇腭裂-外胚层发育不良综合征是一种罕见的常染色体隐性疾病，由编码nectin-1的脊髓灰质炎病毒受体样1（PVRL1）基因的纯合功能丧失突变引起。Nectin-1是一种细胞间粘附分子，对黏着连接和紧密连接形成的起始步骤很重要；它在角质形成细胞、神经元以及发育中的面部和腭部表达。临床表现包括唇腭裂、外胚层发育不良、手指和/或脚趾皮肤并指的独特面部外观，在某些情况下还包括智力迟钝。据我们所知，我们首次报告了一名患有唇腭裂-外胚层发育不良综合征且携带新型PVRL1突变的亚洲个体。一名7岁的日本男孩，是近亲结婚的头胎孩子，表现为少汗性外胚层发育不良，头发稀疏、脆弱、纤细、干燥，牙齿发育不全，唇腭裂的独特面部外观，手指皮肤并指以及轻度智力迟钝。头发的扫描电子显微镜检查显示扭曲发和三角发及管腔发。PVRL1第2外显子的突变分析揭示了一种新型纯合无义突变，c.400C>T（p.Arg134*）。他的父母是突变等位基因的杂合子。迄今为止，在唇腭裂-外胚层发育不良综合征中鉴定出的所有四个PVRL1突变，包括本研究中的突变，都导致了截短的蛋白质，这些蛋白质缺乏nectin-1的跨膜结构域和细胞内结构域，而这是启动细胞间粘附过程所必需 的。
