中华皮肤科杂志 ›› 2020, Vol. 53 ›› Issue (4): 266-270.doi: 10.35541/cjd.20190727

• 论著 • 上一篇    下一篇

着色性干皮病两例ERCC2和ERCC5基因突变分析

杨舟    徐哲    焦磊    王珊    马琳   

  1. 国家儿童医学中心  首都医科大学附属北京儿童医院皮肤科  100045
  • 收稿日期:2019-07-08 修回日期:2020-01-19 发布日期:2020-04-01
  • 通讯作者: 马琳 E-mail:bch_maleen@aliyun.com
  • 基金资助:
    国家自然科学基金（81673042）；北京市医院管理局儿科学科协同发展中心儿科专项（XTZD20180502）

Mutation analysis of the ERCC2 and ERCC5 genes in two cases of xeroderma pigmentosum

Yang Zhou, Xu Zhe, Jiao Lei, Wang Shan, Ma Lin   

  1. Department of Dermatology, Beijing Children′s Hospital, Capital Medical University, National Center for Children′s Health, China, Beijing 100045, China
  • Received:2019-07-08 Revised:2020-01-19 Published:2020-04-01
  • Contact: Ma Lin E-mail:bch_maleen@aliyun.com
  • Supported by:
    National Natural Science Foundation of China （81673042）; Special Fund of the Pediatric Medical Coordinated Development Center of Beijing Municipal Administration of Hospitals （XTZD20180502）

PDF

2

摘要： 【摘要】 目的 分析2例着色性干皮病患儿基因突变。方法 收集2例着色性干皮病患儿临床资料，提取患儿及其父母外周血DNA，采用高通量全外显子组测序方法对患儿进行全外显子组测序，确定致病基因突变位点，再用Sanger测序法对患儿及其父母的DNA进行双向验证，重点关注着色性干皮病相关候选基因XPA、ERCC3、XPC、ERCC2、DDB2、ERCC4、ERCC5及POLH的变异。结果 例1为3岁男孩，面、耳、颈、双手背散发褐色斑点伴色素减退斑2年，步态不稳1年，皮疹夏季加重，以光暴露部位为主。例2为1岁5月龄男孩，面部散发褐色斑点伴少许色素减退斑1年。基因检测显示，例1 ERCC2基因发生复合杂合突变，即父源c.1805G>A（p.Gly602Asp）和母源c.586C>T（p.Arg196Ter）突变，为XPD型。例2 ERCC5基因发生复合杂合突变，即父源c.2533+2T>C和母源c.2453C>T（p.Ala818Val）突变，为XPG型。c.586C>T（p.Arg196Ter）和c.2533+2T>C既往未见报道。嘱防晒、避光，随访2年，患儿皮损较前有所增多，未出现恶性肿瘤。结论 ERCC2基因复合杂合突变可导致XPD型着色性干皮病，表现出皮肤和神经症状；ERCC5基因复合杂合突变可导致XPG型着色性干皮病，表现为轻症表型。早期临床特点结合基因检测有助于着色性干皮病患者的准确诊断及分型。

关键词: 着色性干皮病, DNA突变分析, 皮肤表现, ERCC2基因, ERCC5基因

Abstract: 【Abstract】 Objective To detect gene mutations in two patients with xeroderma pigmentosum （XP）. Methods Clinical data were collected from two patients with XP. DNA was extracted from peripheral blood of the patients and their parents, and high-throughput whole-exome sequencing was performed in the patient to identify pathogenic gene mutations. Then, Sanger sequencing was performed to bidirectionally verify the mutations in the patients and their parents, with a focus on mutations in the candidate genes XPA, ERCC3, XPC, ERCC2, DDB2, ERCC4, ERCC5 and POLH. Results Case 1, a 3-year-old male patient, presented with brown spots and hypopigmented macules on the face, ears, neck and back of both hands for 2 years, as well as gait instability for 1 year. The skin lesions were mainly distributed in sun-exposed areas and worsened in summer. Case 2, a male patient aged 1 year and 5 months, presented with scattered brown spots and a few hypopigmented macules on the face for 1 year. Genetic testing showed compound heterozygous mutations in the ERCC2 gene of case 1, including c.1805G>A （p.Gly602Asp） mutation inherited from his father and c.586C>T （p.Arg196Ter） mutation inherited from the his mother, so case 1 was diagnosed with XP group D （XPD）. Compound heterozygous mutations were identified in the ERCC5 gene of case 2, including c.2533+2T>C mutation inherited from his father and c.2453C>T（p.Ala818Val）mutation inherited from his mother, so case 2 was diagnosed with XP group G （XPG）. The c.586C>T（p.Arg196Ter）and c.2533+2T>C mutations had not been reported before. Sun protection was suggested. After a follow-up of 2 years, skin lesions increased in the 2 patients, but no malignant tumors occurred. Conclusions The compound heterozygous mutations in the ERCC2 gene can lead to XPD, mainly manifesting as cutaneous and neurological symptoms, while the compound heterozygous mutations in the ERCC5 gene can lead to XPG, manifesting as a mild phenotype. Early clinical features combined with genetic testing are helpful for accurate diagnosis and classification of XP.

Key words: Xeroderma pigmentosum, DNA mutational analysis, Skin manifestations, ERCC2 gene, ERCC5 gene

引用本文

杨舟 徐哲 焦磊 王珊 马琳. 着色性干皮病两例ERCC2和ERCC5基因突变分析[J]. 中华皮肤科杂志, 2020,53(4):266-270. doi:10.35541/cjd.20190727

Yang Zhou, Xu Zhe, Jiao Lei, Wang Shan, Ma Lin. Mutation analysis of the ERCC2 and ERCC5 genes in two cases of xeroderma pigmentosum[J]. Chinese Journal of Dermatology, 2020, 53(4): 266-270.doi:10.35541/cjd.20190727