两个营养不良型大疱性表皮松解症家系的基因诊断

doi:10.35541/cjd.20220061

中华皮肤科杂志 ›› 2023, Vol. 56 ›› Issue (8): 770-773.doi: 10.35541/cjd.20220061

两个营养不良型大疱性表皮松解症家系的基因诊断

王莉¹ 任增果² 娄桂予¹ 张玉薇¹ 杨科¹ 雷星星¹ 张冰¹ 廖世秀¹ 郝冰涛¹

¹河南省人民医院医学遗传研究所郑州大学人民医院河南大学人民医院，郑州 450003；²河南大学人民医院医学遗传研究所河南省人民医院，郑州 450003

收稿日期:2022-01-24 修回日期:2022-10-13 发布日期:2023-08-07
通讯作者: 王莉 E-mail:wanglily@zzu.edu.cn
基金资助:
河南省医学科技攻关计划项目（2018020388）

Genetic diagnosis in two families with dystrophic epidermolysis bullosa

Wang Li¹, Ren Zengguo², Lou Guiyu¹, Zhang Yuwei¹, Yang Ke¹, Lei Xingxing¹, Zhang Bing¹, Liao Shixiu¹, Hao Bingtao¹

¹Henan Institute of Medical Genetics, Henan Provincial People′s Hospital, Zhengzhou University People′s Hospital, Henan University People′s Hospital, Zhengzhou 450003, Henan; ²Henan Institute of Medical Genetics, Henan University People′s Hospital, Henan Provincial People′s Hospital, Zhengzhou 450003, Henan

Received:2022-01-24 Revised:2022-10-13 Published:2023-08-07
Contact: Wang Li E-mail:wanglily@zzu.edu.cn
Supported by:
Medical Science and Technology Project of Henan Province（2018020388）

摘要/Abstract

摘要： 【摘要】目的分析两个营养不良型大疱性表皮松解症家系的临床特点和致病基因，揭示疾病的发生机制和患者表型差异机制。方法从两家系成员的外周血中提取DNA进行高通量测序及Sanger测序验证。结果临床资料分析显示，2个家系先证者的临床表现符合营养不良型大疱性表皮松解症的诊断，其中家系1先证者症状明显重于家系中其他患者。基因测序结果显示，家系1患者均携带COL7A1基因c.6082G>C（p.G2028R）突变，同时先证者及其表型正常的母亲和舅舅还携带该基因致病性剪切位点突变c.7068+2（IVS91）T>G，为首次报道致病突变。家系2先证者携带COL7A1基因c.6081_6082 ins C（p. G2028Rfs*71）突变和首次报道的c.1892 G>A（p.W631X）突变，分别来自其父母。结论家系1先证者同时携带2个致病突变可能是其严重临床表型的分子机制；首次报道的COL7A1基因突变丰富了该基因突变谱。

关键词: 大疱性表皮松解, 结合性, DNA突变分析, 皮肤表现, 外显子组测序, COL7A1基因

Abstract: 【Abstract】 Objective To analyze clinical characteristics of and causative genes in two families with dystrophic epidermolysis bullosa, and to reveal the pathogenesis of the disease and mechanisms underlying phenotypic differences between patients. Methods DNA was extracted from peripheral blood samples of two family members, and subjected to high-throughput sequencing and Sanger sequencing. Results The clinical manifestations of the 2 probands in the 2 families were consistent with the diagnosis of dystrophic epidermolysis bullosa, and the symptoms of the proband in family 1 were more serious than those of other patients in the family. Genetic testing showed that all patients in family 1 carried a mutation c.6082G>C （p.G2028R） in the COL7A1 gene, and the proband and her phenotypically normal mother and uncle also carried a splice-site mutation c.7068+2 （IVS91） T>G in the COL7A1 gene, both of which were first reported. The proband in family 2 carried a mutation c.6081_6082 ins C （p.G2028Rfs*71） and the first reported mutation c.1892G>A （p.W631X） in the COL7A1 gene, which were inherited from her father and mother, respectively. Conclusion The two pathogenic mutations may be the molecular mechanism underlying the severe clinical phenotype in the proband in family 1; the first reported mutations enriched the mutation spectrum of the COL7A1 gene.

Key words: Epidermolysis bullosa, junctional, DNA mutational analysis, Skin manifestations, Whole exome sequencing, COL7A1 gene

王莉任增果娄桂予张玉薇杨科雷星星张冰廖世秀郝冰涛. 两个营养不良型大疱性表皮松解症家系的基因诊断[J]. 中华皮肤科杂志, 2023,56(8):770-773. doi:10.35541/cjd.20220061

Wang Li, Ren Zengguo, Lou Guiyu, Zhang Yuwei, Yang Ke, Lei Xingxing, Zhang Bing, Liao Shixiu, Hao Bingtao. Genetic diagnosis in two families with dystrophic epidermolysis bullosa[J]. Chinese Journal of Dermatology, 2023, 56(8): 770-773.doi:10.35541/cjd.20220061

参考文献 15

［1］	Dang N, Murrell DF. Mutation analysis and characterization of COL7A1 mutations in dystrophic epidermolysis bullosa［J］. Exp Dermatol, 2008,17（7）:553⁃568. doi: 10.1111/j.1600⁃0625.2008. 00723.x.
［2］	COL7A1与PLEC双基因突变致大疱性表皮松解症一例国内首报［J］. 中华皮肤科杂志, 2020,53（4）:275⁃278. doi: 10. 35541/cjd.20190576.
［3］	Shinkuma S. Dystrophic epidermolysis bullosa: a review［J］. Clin Cosmet Investig Dermatol, 2015,8:275⁃284. doi: 10.2147/CCID.S54681.
［4］	Mohammedi R, Mellerio JE, Ashton GH, et al. A recurrent COL7A1 mutation, R2814X, in British patients with recessive dystrophic epidermolysis bullosa［J］. Clin Exp Dermatol, 1999,24（1）:37⁃39. doi: 10.1046/j.1365⁃2230.1999.00404.x.
［5］	Ben Brick AS, Laroussi N, Mesrati H, et al. Mutational founder effect in recessive dystrophic epidermolysis bullosa families from Southern Tunisia［J］. Arch Dermatol Res, 2014,306（4）:405⁃411. doi: 10.1007/s00403⁃013⁃1421⁃y.
［6］	Tamai K, Murai T, Mayama M, et al. Recurrent COL7A1 mutations in Japanese patients with dystrophic epidermolysis bullosa: positional effects of premature termination codon mutations on clinical severity. Japanese Collaborative Study Group on Epidermolysis Bullosa［J］. J Invest Dermatol, 1999,112（6）:991⁃993. doi: 10.1046/j.1523⁃1747.1999.00601.x.
［7］	Mellerio JE, Salas⁃Alanis JC, Talamantes ML, et al. A recurrent glycine substitution mutation, G2043R, in the type VII collagen gene （COL7A1） in dominant dystrophic epidermolysis bullosa［J］. Br J Dermatol, 1998,139（4）:730⁃737. doi: 10.1046/j.1365⁃2133.1998.02496.x.
［8］	Nagai M, Nagai H, Tominaga C, et al. Localised dominant dystrophic epidermolysis bullosa with a novel de novo mutation in COL7A1 diagnosed by next⁃generation sequencing［J］. Acta Derm Venereol, 2015,95（5）:629⁃631. doi: 10.2340/00015555⁃2019.
［9］	Lee JY, Li C, Chao SC, et al. A de novo glycine substitution mutation in the collagenous domain of COL7A1 in dominant dystrophic epidermolysis bullosa［J］. Arch Dermatol Res, 2000,292（4）:159⁃163. doi: 10.1007/s004030050472.
［10］	Murata T, Masunaga T, Shimizu H, et al. Glycine substitution mutations by different amino acids in the same codon of COL7A1 lead to heterogeneous clinical phenotypes of dominant dystrophic epidermolysis bullosa［J］. Arch Dermatol Res, 2000,292（10）:477⁃481. doi: 10.1007/s004030000162.
［11］	Iwata T, Nakano H, Nakano A, et al. Dominant dystrophic epidermolysis bullosa caused by a novel G2037R mutation and by a known G2028R mutation in the type VII collagen gene （COL7A1）［J］. J Dermatol, 2006,33（8）:550⁃556. doi: 10.1111/j.1346⁃8138.2006.00130.x.
［12］	Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology［J］. Genet Med, 2015,17（5）:405⁃424. doi: 10.1038/gim.2015.30.
［13］	Almaani N, Liu L, Dopping⁃Hepenstal PJ, et al. Identical glycine substitution mutations in type VII collagen may underlie both dominant and recessive forms of dystrophic epidermolysis bullosa［J］. Acta Derm Venereol, 2011,91（3）:262⁃266. doi: 10.2340/00015555⁃1053.
［14］	Pfendner EG, Nakano A, Pulkkinen L, et al. Prenatal diagnosis for epidermolysis bullosa: a study of 144 consecutive pregnancies at risk［J］. Prenat Diagn, 2003,23（6）:447⁃456. doi: 10.1002/pd.619.
［15］	Chong SC, Hon KL, Yuen L, et al. Neonatal epidermolysis bullosa: lessons to learn about genetic counseling［J］. J Dermatolog Treat, 2021,32（1）:29⁃32. doi: 10.1080/09546634. 2018.1527999.

[1]	陈春里闫思聿王丹高丽华谭丽娜唐四元刘伟曾金容鲁建云. 酸化脂肪酸酯治疗特应性皮炎样模型小鼠的疗效及机制初探[J]. 中华皮肤科杂志, 2023, 56(9): 822-831.
[2]	贾韬宋相瑾耿松梅. 自身炎症性皮肤病[J]. 中华皮肤科杂志, 2023, 56(8): 794-799.
[3]	李越吴金燕袁若月杨屈杨赵贤省朱宁文. 细胞治疗遗传性大疱性表皮松解症研究进展[J]. 中华皮肤科杂志, 2023, 56(7): 698-702.
[4]	宋德宇王嘉玥耿佳邹美熔李仲桃陈玉沙汪盛. GJB2基因p.N54H突变致经典型Vohwinkel综合征1例[J]. 中华皮肤科杂志, 2023, 56(7): 669-672.
[5]	李翔倩赵永平赵梦曦周城. LSS基因突变导致先天性少毛症14型1家系[J]. 中华皮肤科杂志, 2023, 56(7): 672-676.
[6]	黄晓燕肖易敬丹榕陈明亮沈敏学. 湖南省某砷尾矿地区居民砷中毒皮肤损害患病率及相关因素调查[J]. 中华皮肤科杂志, 2023, 56(7): 636-641.
[7]	魏瑾闫会文赵天威冉立伟伦文辉张建中. 乳头乳晕湿疹样透明细胞棘皮瘤：国内首报及文献分析[J]. 中华皮肤科杂志, 2023, 56(6): 545-548.
[8]	任发亮王华肖异珠. 透明细胞丘疹病57例临床特征分析[J]. 中华皮肤科杂志, 2023, 56(4): 309-312.
[9]	万立胡彬罗红玉方美珍韩丽娟陈强周小勇陈柳青陈金波. 天疱疮或大疱性类天疱疮合并单纯疱疹病毒感染8例临床特征及治疗分析[J]. 中华皮肤科杂志, 2023, 56(3): 229-233.
[10]	王媛丽刘玲孙中斌李凯. 临床误诊为黑素瘤的其他疾病141例分析[J]. 中华皮肤科杂志, 2023, 56(3): 244-246.
[11]	于灵窦进法王建波张守民. 常染色体显性Waardenburg综合征1家系基因突变分析[J]. 中华皮肤科杂志, 2023, 56(3): 241-243.
[12]	邓磷君涂平. 玫瑰糠疹110例组织病理分析[J]. 中华皮肤科杂志, 2023, 0(3): 20220130-e20220130.
[13]	李巍李政. 【开放获取】典型与非典型表现的特应性皮炎[J]. 中华皮肤科杂志, 2023, 56(1): 1-4.
[14]	顾安康张宇马法库孔祥君张理涛. 游泳池肉芽肿56例临床病理分析[J]. 中华皮肤科杂志, 2022, 55(9): 795-798.
[15]	刘晨美陈鸿裕陈平姣曾抗李常兴. 眼皮肤白化病1家系致病基因鉴定[J]. 中华皮肤科杂志, 2022, 55(8): 706-709.

两个营养不良型大疱性表皮松解症家系的基因诊断

Genetic diagnosis in two families with dystrophic epidermolysis bullosa

PDF

PDF (Mobile)

可视化

摘要/Abstract

引用本文

使用本文

参考文献 15

相关文章 15

Metrics

本文评价

推荐阅读 10