Gao Yajuan, Zhang Qianli, Zhang Shiyu, Yang Lu, Liu Yaping, Liu Yuehua, Wang Tao
State Key Laboratory of Complex Severe and Rare Diseases, Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China.
Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Front Genet. 2022 May 23;13:797124. doi: 10.3389/fgene.2022.797124. eCollection 2022.
Gap junctions formed by connexins are channels on cytoplasm functioning in ion recycling and homeostasis. Some members of connexin family including connexin 31 are significant components in human skin and cochlea. In clinic, mutations of connexin 31 have been revealed as the cause of a rare hereditary skin disease called erythrokeratodermia variabilis (EKV) and non-syndromic hearing loss (NSHL). To determine the underlying genetic cause of EKV, ichthyosis and NSHL in three members of a Chinese pedigree and skin histologic characteristics of the EKV patient. By performing whole exome sequencing (WES), Sanger sequencing and skin biopsy, we demonstrate a Chinese pedigree carrying a mutation of with three patients separately diagnosed with EKV, ichthyosis and NSHL. The proband, a 6-year-old Chinese girl, presented with demarcated annular red-brown plaques and hyperkeratotic scaly patches on her trunk and limbs. Her mother has ichthyosis with hyperkeratosis and geographic tongue while her younger brother had NSHL since birth. Mutation analysis revealed all of them carried a heterozygous missense mutation c.293G>A of . Skin biopsy showed many grain cells with dyskeratosis in the granular layer. Acanthosis, papillomatosis, and a mild superficial perivascular lymphocytic infiltrate were observed. A mutation of associated with EKV, ichthyosis and NSHL is reported in this case. The daughter with EKV and the son with NSHL in this Chinese family inherited the mutation from their mother with ichthyosis. The variation of clinical features may involve with genetic, epigenetic and environmental factors.
由连接蛋白形成的间隙连接是细胞质中负责离子循环和内稳态的通道。连接蛋白家族的一些成员，包括连接蛋白31，是人类皮肤和耳蜗的重要组成部分。在临床上，已发现连接蛋白31的突变是一种罕见的遗传性皮肤病——可变性红斑角皮病（EKV）和非综合征性听力损失（NSHL）的病因。为了确定一个中国家系中三名成员患EKV、鱼鳞病和NSHL的潜在遗传原因以及EKV患者的皮肤组织学特征。通过进行全外显子组测序（WES）、桑格测序和皮肤活检，我们证实了一个携带突变的中国家系，其中三名患者分别被诊断为EKV、鱼鳞病和NSHL。先证者是一名6岁的中国女孩，其躯干和四肢出现边界清晰的环形红棕色斑块和角化过度的鳞屑斑。她的母亲患有伴有角化过度的鱼鳞病和地图舌，而她的弟弟自出生以来就患有NSHL。突变分析显示他们都携带了杂合错义突变c.293G>A。皮肤活检显示颗粒层有许多角化不良的谷粒细胞。观察到棘层肥厚、乳头瘤样增生和轻度浅表血管周围淋巴细胞浸润。本病例报告了一种与EKV、鱼鳞病和NSHL相关的突变。这个中国家庭中患EKV的女儿和患NSHL的儿子从患有鱼鳞病的母亲那里继承了该突变。临床特征的差异可能涉及遗传、表观遗传和环境因素。
