显性营养不良型大疱性表皮松解症一家系COL7A1基因错义突变分析  

Missense mutation analysis of the COL7A1 gene in a pedigree with dominant dystrophic epidermolysis bullosa

作　　者：余林洪 王怀玉 朱长华 董琳馨 吴保凤 林立航[1] 肖学敏[1] Yu Linhong;Wang huaiyu;Zhu Changhua;Dong Linxin;Wu Baofeng;Lin Lihang;Xiao Xuemin(Department of Dermatology,Fujian Medical University Union Hospital,Fuzhou 350001,China)

机构地区：[1]福建医科大学附属协和医院皮肤科,福州350001 [2]福建医科大学附属协和医院

出　　处：《中华皮肤科杂志》2024年第5期455-458,共4页Chinese Journal of Dermatology

基　　金：福建省医学创新课题(2022CXA013)。

摘　　要：目的检测1个显性营养不良型大疱性表皮松解症家系基因突变情况。方法先证者男,20岁,自出生后四肢反复出现水疱、破溃、色素沉着、瘢痕、指(趾)甲变形等。该家系3代共5例患者,均有典型皮损。提取该家系14名成员(包括5例患者)和100名无亲缘关系健康对照的外周血标本,对先证者行全外显子组测序,选定相关的突变位点,在家系中用Sanger测序验证该突变位点。结果基因测序示,先证者及其他4例患者COL7A1基因的第107号外显子均存在错义突变(c.7885G>A),导致第2629位氨基酸由甘氨酸变为精氨酸(p.G2629R),9名健康亲属和100名健康对照未发现该突变。该家系中该突变与显性营养不良型大疱性表皮松解症共分离,在Pubmed、HGMD、ClinVar等多种数据库查询未见收录,考虑该突变为新发错义突变,其编码的氨基酸改变VI型胶原蛋白结构,从而影响蛋白功能。结论在该显性营养不良型大疱性表皮松解症家系COL7A1基因107号外显子发现了新的错义突变,扩展了COL7A1基因突变数据库。Objective To detect gene mutations in a pedigree with dominant dystrophic epidermolysis bullosa(DDEB).Methods A 20-year-old male proband presented with repeated blisters,ulceration,pigmentation,scars on the limbs,and deformation of the nails/toenails after birth.There were 5 patients in the 3-generation family,and they all presented with typical skin lesions.Peripheral blood samples were obtained from 14 members of the pedigree(including the 5 patients)and 100 unrelated healthy controls.Whole-exome sequencing was performed in the proband to identify relevant mutation sites,which were then confirmed in the family by Sanger sequencing.Results Genetic testing indicated that the proband and the other 4 patients all carried a missense mutation(c.7885G>A)in exon 107 of the COL7A1 gene,resulting in the substitution of glycine by arginine at amino acid position 2629(p.G2629R).The mutation was identified neither in the 9 healthy relatives nor in the 100 unrelated healthy controls.The mutation co-segregated with DDEB in the family,and was not included in databases such as Pubmed,HGMD or ClinVar,suggesting it was a novel missense mutation.The amino acid encoded by this mutation may alter the structure of type V collagen,thereby affecting its function.Conclusion A novel missense mutation was identified in exon 107 of the COL7A1 gene in the family with DDEB,expanding the spectrum of mutations in the COL7A1 gene.

关 键 词：表皮松解 大疱性 营养不良性 DNA突变分析 COL7A1基因 错义突变 

分 类 号：R758.59[医药卫生—皮肤病学与性病学]