先天性少毛症一例致病基因突变研究  

Mutation analysis of causative genes in a case of congenital hypotrichosis

作　　者：周娜 史传奎 张开慧 刘毅 盖中涛 

机构地区：[1]山东大学齐鲁儿童医院儿科医学研究所,济南250022 [2]山东大学齐鲁儿童医院皮肤科,济南250022

出　　处：《中华皮肤科杂志》2017年第11期820-824,共5页Chinese Journal of Dermatology

摘　　要：目的 通过新一代测序技术，在分子水平明确1例先天性少毛症患儿遗传学病因。方法 患儿女，9岁3个月，出生即头发少，呈绒毛状，生长缓慢。皮肤科检查示头发细软呈淡黄色、羊毛状，稀疏，头顶发量稍多，四周发量稀少，发际线上移，前额增宽。眼科检查无明显异常。患儿父母及妹妹均无相似异常表型，患儿父母非近亲结婚。抽取患儿及其母亲、妹妹外周静脉血，对基因组DNA进行新一代测序分析，并对疑似致病性突变位点进行Sanger测序验证及生物信息学分析。结果 患儿CDH3基因存在2个突变，分别是第5号外显子c.1057G 〉 T（p.D353Y）杂合突变和第10号外显子c.1767delC（p.I589Ifs）杂合突变，均为新突变，软件预测具有致病性。Sanger测序验证示c.1057G 〉 T（p.D353Y）杂合突变来自患儿母亲；传递分析示c.1767delC（p.I589Ifs）杂合突变来自患儿父亲。结论 该先天性少毛症患儿携带的c.1057G 〉 T（p.D353Y）和c.1767delC（p.I589Ifs）杂合突变可能导致其发生先天性少毛症伴青少年黄斑营养不良，应严密观察并按时进行全面眼科检查，以便及时发现并尽早对症治疗眼部症状。Objective To identify the genetic cause of a case of congenital hypotrichosis by a next-generation sequencing technology. Methods A 9-year and 3-month-old girl presented with few villous hairs at birth, which grew slowly. Skin examination showed sparse, thin, soft, woolly and light-yellow hairs, small amount of hairs on the top of the head and a less amount of hairs around the head, hairline recession and broadened forehead. No abnormality was found by ophthalmic examination. No similar aberrant phenotype was observed in the patient′s parents or her younger sister. Her parents were non-consanguineous marriage. Peripheral venous blood samples were obtained from the patient, her mother and younger sister. Genomic DNA was extracted and then analyzed by a next-generation sequencing technology. The suspected pathogenic mutations were validated by Sanger sequencing and subjected to bioinformatics analysis. Results Two mutations were identified in the CDH3 gene in the patient, including a c.1057G 〉 T （p.D353Y） heterozygous mutation in exon 5 and a c.1767delC （p.I589Ifs） heterozygous mutation in exon 10. They were both novel mutations, and their pathogenicity was predicted by softwares. Sanger sequencing indicated that the c.1057G 〉 T （p.D353Y） heterozygous mutation was inherited from the patient′s mother, and gene transfer analysis revealed that the c.1767delC （p.I589Ifs） heterozygous mutation was inherited from the patient′s father. Conclusion The c.1057G 〉 T （p.D353Y） and c.1767delC （p.I589Ifs） heterozygous mutations may cause hypotrichosis and juvenile macular dystrophy in the patient, so careful observation and comprehensive ophthalmic examination should be performed on time for early diagnosis and treatment of eye symptoms.

关 键 词：稀毛症 突变 DNA突变分析 CDH3基因 

分 类 号：R758.71[医药卫生—皮肤病学与性病学]