Han Yang, Wang Xiuli, Zheng Liyun, Zhu Tingting, Li Yuwei, Hong Jiaqi, Xu Congcong, Wang Peiguang, Gao Min
Department of Dermatology of First Affiliated Hospital, First Affiliated Hospital of Anhui Medical University, Hefei, China.
Institute of Dermatology, Anhui Medical University, Hefei, China.
Front Genet. 2020 Feb 4;11:21. doi: 10.3389/fgene.2020.00021. eCollection 2020.
This study aimed to investigate the genetic causes of hypohidrotic ectodermal dysplasia (HED) in two families and elucidate the molecular pathogenesis of HED in Chinese Han patients.
Whole-exome sequencing (WES) was used to screen HED-related genes in two family members, followed by confirmatory Sanger sequencing. Bioinformatics analysis was performed for the mutations. We reviewed HED-related articles in PubMed. - and Fisher's tests were used to analyze the genotype-phenotype correlations.
(1) WES identified missense mutations [c.1127 C > T (p.T376M; NM_001005609)] in family 1 and an nonframeshift deletion mutation [c.648_683delACCTGGTCCTCCAGGTCCTCCTGGTCCTCAAGGACC (p.216_228delPPGPPGPPGPQGP; NM_001005609)] in family 2. Sanger sequencing validated the results. ANNOVAR (ANNOtate VARiation) annotation indicated that c.1127 c > T was a deleterious mutation. (2) The review of published papers revealed 68 novel mutations related to HED: 57 (83.8%) were mutations, 8 (11.8%) were mutations, 2 (2.9%) were mutations, 1 (1.5%) was a mutation, 31 (45.6%) were missense mutations, 23 (33.8%) were deletion mutations, and 1 (1.5%) was an indel. Genotype-phenotype correlation analysis revealed that patients with missense mutations had a higher frequency of hypohidrosis (P = 0.021).
This study identified two gene mutations in two Chinese Han HED families and provides a foundation for genetic diagnosis and counseling.
本研究旨在调查两个家庭中少汗型外胚层发育不良（HED）的遗传原因，并阐明中国汉族患者中HED的分子发病机制。
采用全外显子组测序（WES）对两个家庭成员进行HED相关基因筛查，随后进行验证性桑格测序。对突变进行生物信息学分析。我们在PubMed上检索了与HED相关的文章。采用卡方检验和Fisher检验分析基因型与表型的相关性。
（1）WES在家庭1中鉴定出错义突变[c.1127 C>T（p.T376M；NM_001005609）]，在家庭2中鉴定出一个非移码缺失突变[c.648_683delACCTGGTCCTCCAGGTCCTCCTGGTCCTCAAGGACC（p.216_228delPPGPPGPPGPQGP；NM_001005609）]。桑格测序验证了结果。ANNOVAR（注释变异）注释表明c.1127 c>T是一个有害突变。（2）对已发表论文的综述揭示了68个与HED相关的新突变：57个（83.8%）是错义突变，8个（11.8%）是无义突变，2个（2.9%）是剪接突变，1个（1.5%）是终止密码子突变，31个（45.6%）是错义突变，23个（33.8%）是缺失突变，1个（1.5%）是插入缺失突变。基因型与表型相关性分析显示，错义突变患者少汗症发生率较高（P = 0.021）。
本研究在中国汉族HED家庭中鉴定出两个EDA基因突变，为遗传诊断和咨询提供了基础。
