KRT5基因新生突变致重度型单纯型大疱性表皮松解症一家系

doi:10.35541/cjd.20200315

中华皮肤科杂志 ›› 2021, Vol. 54 ›› Issue (3): 229-231.doi: 10.35541/cjd.20200315

KRT5基因新生突变致重度型单纯型大疱性表皮松解症一家系

王小坡¹ 陈志明² 杨勇² 孙建方¹

¹中国医学科学院、北京协和医学院皮肤病医院病理科，南京 210042；²中国医学科学院、北京协和医学院皮肤病医院遗传病中心，南京 210042

收稿日期:2020-04-01 修回日期:2020-06-17 发布日期:2021-03-02
通讯作者: 孙建方 E-mail:fangmin5758@aliyun.com
基金资助:
中国医学科学院医学与健康科技创新工程项目;南京市国家级临床医学中心培育计划项目

A family of severe epidermolysis bullosa simplex caused by a de novo mutation in the KRT5 gene

Wang Xiaopo¹, Chen Zhiming², Yang Yong², Sun Jianfang¹

¹Department of Pathology, Hospital of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China; ²Genetic Skin Disease Center, Hospital of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China

Received:2020-04-01 Revised:2020-06-17 Published:2021-03-02
Contact: Sun Jianfang E-mail:fangmin5758@aliyun.com
Supported by:
CAMS Innovation Fund for Medical Sciences;Nanjing Incubation Program for National Clinical Research Center

摘要/Abstract

摘要： 【摘要】目的报道1例重度型单纯型大疱性表皮松解症，并检测其基因突变。方法收集患者及其父母资料和外周血，提取基因组DNA，全外显子组测序筛查患儿致病基因，随后采用Sanger测序对家系成员进行验证。结果患者KRT5基因第7号外显子第1 429位碱基发生G→A（c.1429G>A）杂合突变，导致KRT5基因所编码的蛋白第477位谷氨酸转换成赖氨酸（p.Glu477Lys），其父母未发现该突变。结论该例重度型单纯型大疱性表皮松解症患者存在KRT5基因c.1429G>A（p.Glu477Lys）致病突变，属新生突变。

关键词: 单纯性大疱性表皮松解, DNA突变分析, 角蛋白5, KRT5基因

Abstract: 【Abstract】 Objective To detect genetic mutations in a case of severe epidermolysis bullosa simplex. Methods Clinical data and peripheral blood samples were collected from the patient and her parents, and genomic DNA was extracted. Whole exome sequencing was performed to identify causative gene mutations in the patient, and then Sanger sequencing to verify the mutations among the family members. Results A heterozygous mutation c.1429G>A at position 1429 in exon 7 of the KRT5 gene was identified in the patient, which led to the substitution of glutamic acid by lysine at amino acid position 477 （p.Glu477Lys） of keratin 5 encoded by the KRT5 gene. The mutation was not detected in her unaffected parents. Conclusion A causative mutation c.1429G>A （p.Glu477Lys） in the KRT5 gene was identified in the patient with severe epidermolysis bullosa simplex, which was a de novo mutation.

Key words: Epidermolysis bullosa simplex, DNA mutational analysis, Keratin-5, KRT5 gene

王小坡陈志明杨勇孙建方. KRT5基因新生突变致重度型单纯型大疱性表皮松解症一家系[J]. 中华皮肤科杂志, 2021,54(3):229-231. doi:10.35541/cjd.20200315

Wang Xiaopo, Chen Zhiming, Yang Yong, Sun Jianfang . A family of severe epidermolysis bullosa simplex caused by a de novo mutation in the KRT5 gene[J]. Chinese Journal of Dermatology, 2021, 54(3): 229-231.doi:10.35541/cjd.20200315

参考文献 15

［1］	Bolling MC, Lemmink HH, Jansen GH, et al. Mutations in KRT5 and KRT14 cause epidermolysis bullosa simplex in 75% of the patients［J］. Br J Dermatol, 2011,164（3）:637⁃644. doi: 10.1111/j.1365⁃2133.2010.10146.x.
［2］	Has C, Bauer JW, Bodemer C, et al. Consensus reclassification of inherited epidermolysis bullosa and other disorders with skin fragility［J］. Br J Dermatol, 2020. doi: 10.1111/bjd.18921.
［3］	Müller FB, Küster W, Wodecki K, et al. Novel and recurrent mutations in keratin KRT5 and KRT14 genes in epidermolysis bullosa simplex: implications for disease phenotype and keratin filament assembly［J］. Hum Mutat, 2006,27（7）:719⁃720. doi: 10.1002/humu.9437.
［4］	Kim EN, Harris AG, Bingham LJ, et al. A review of 52 pedigrees with epidermolysis bullosa simplex identifying ten novel mutations in KRT5 and KRT14 in Australia［J］. Acta Derm Venereol, 2017,97（9）:1114⁃1119. doi: 10.2340/00015555⁃2715.
［5］	杨建强. Dowling⁃Meara亚型单纯型大疱性表皮松解症基因突变分析［J］. 临床医学工程, 2012,19（9）:1470⁃1471,1474. doi: 10.3969/j.issn.1674⁃4659.2012.09.1470.
［6］	谭燕红, 林志淼, 王建才, 等. 角蛋白14突变导致Dowling⁃Meara亚型单纯型大疱性表皮松解症伴色素沉着［J］. 临床皮肤科杂志, 2011,40（4）:203⁃205. doi: 10.3969/j.issn.1000⁃4963. 2011.04.007.
［7］	李建国, 艾豫蜀, 李振鲁, 等. 单纯型大疱性表皮松解症一家系K14基因突变的检测［J］. 临床皮肤科杂志, 2011,40（2）:76⁃77. doi: 10.3969/j.issn.1000⁃4963.2011.02.005.
［8］	吴佳纹, 肖生祥, 王俊民, 等. 单纯型大疱性表皮松解症Dowling⁃Mesa亚型基因突变检测［J］. 中国皮肤性病学杂志, 2009,23（7）:393⁃394.
［9］	赵亚力, 韩为东, 马学斌, 等. Dowling⁃Meara型单纯性大疱性表皮松解症一家系角蛋白基因突变研究［J］. 军医进修学院学报, 2005,26（1）:49⁃51. doi: 10.3969/j.issn.1005⁃1139.2005. 01.020.
［10］	杨勇, 李冠群, 朱学骏. Dowling⁃Meara亚型单纯型大疱性表皮松解症一家系的基因突变检测［J］. 中华皮肤科杂志, 2001,34（1）:36⁃38. doi: 10.3760/j.issn:0412⁃4030.2001.01.010.
［11］	Lalor L, Titeux M, Palisson F, et al. Epidermolysis bullosa simplex⁃generalized severe type due to keratin 5 p.Glu477Lys mutation: genotype⁃phenotype correlation and in silico modeling analysis［J］. Pediatr Dermatol, 2019,36（1）:132⁃138. doi: 10. 1111/pde.13722.
［12］	Schumann H, Roth W, Has C, et al. Verrucous carcinoma in epidermolysis bullosa simplex is possibly associated with a novel mutation in the keratin 5 gene［J］. Br J Dermatol, 2012,167（4）:929⁃936. doi: 10.1111/j.1365⁃2133.2012.11075.x.
［13］	Hamada T, Kawano Y, Szczecinska W, et al. Novel keratin 5 and 14 gene mutations in patients with epidermolysis bullosa simplex from Poland［J］. Arch Dermatol Res, 2005,296（12）:577⁃579. doi:10.1007/s00403⁃005⁃0560⁃1.
［14］	Sathishkumar D, Orrin E, Terron⁃Kwiatkowski A, et al. The p.Glu477Lys mutation in keratin 5 is strongly associated with mortality in generalized severe epidermolysis bullosa simplex［J］. J Invest Dermatol, 2016,136（3）:719⁃721. doi: 10.1016/j.jid.2015.11.024.
［15］	Komori T, Dainichi T, Masuno Y, et al. p.Glu477Lys mutation in keratin 5 is not necessarily mortal in generalized severe epidermolysis bullosa simplex［J］. J Dermatol, 2018,45（8）:e209⁃e210. doi: 10.1111/1346⁃8138.14258.

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KRT5基因新生突变致重度型单纯型大疱性表皮松解症一家系

A family of severe epidermolysis bullosa simplex caused by a de novo mutation in the KRT5 gene

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