中国麻风皮肤病杂志 ›› 2024, Vol. 40 ›› Issue (4): 234-238.doi: 10.12144/zgmfskin202404234

• 论著 • 上一篇    下一篇

常染色体隐性遗传性羊毛状发伴少毛症两家系基因突变分析

赵安琪1,2,曹巧玉3,郑璐瑶4,刘庆梅5,李明3,吴文育5,赵敬军1,2   

  1. 1上海交通大学医学院附属新华医院皮肤科，上海，200092；2上海交通大学医学院皮肤病研究所，上海，200092；3复旦大学附属儿科医院皮肤科，上海，201102；4安徽省儿童医院皮肤科，安徽合肥，230022；5复旦大学附属华山医院皮肤科，上海，200040
  • 出版日期:2024-04-15 发布日期:2024-03-26

Mutation analysis in two families with autosomal recessive woolly hair with hypotrichosis

ZHAO Anqi1,2, CAO Qiaoyu3, ZHENG Luyao4, LIU Qingmei5, LI Ming3, WU Wenyu5, ZHAO Jingjun1,2   

  1. 1 Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China; 2 Institute of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China; 3 Department of Dermatology, The Children's Hospital of Fudan University, Shanghai 201102, China; 4 Department of Dermatology, Anhui Provincial Children's Hospital, Hefei 230022, China; 5 Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China
  • Online:2024-04-15 Published:2024-03-26

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摘要： 目的：检测常染色体隐性遗传性羊毛状发伴少毛患者家系的致病基因。方法：收集2例中国汉族常染色体隐性遗传性羊毛状发伴少毛家系患者及其父母外周血标本，应用二代皮肤靶向测序包检测血样中DNA的基因突变，Sanger测序进行家系验证，Minigene验证剪切突变致病性。结果：先证者1的LIPH基因检测到c.742C>A（p.His248Asn）和c.982+12A>G的复合杂合突变。先证者2的LIPH基因检测到c.629-1_629delinsTT和c.686delAinsGTAGAACCCAACCTGGCT的复合杂合突变。一代测序验证显示复合杂合突变分别来自母亲和父亲。LIPH c.982+12A>G和c.629-1_629delinsTT尚未报道过，Minigene验证发现，剪切突变c.982+12A>G会导致内含子滞留；剪切突变c.629-1_629delinsTT会导致外显子跳跃和外显子缺失。结论：本文报道了LIPH的两个新剪切突变，通过家系验证和Minigene验证了剪切突变的致病性，丰富了LIPH导致常染色体隐性羊毛状发伴少毛的突变谱。

关键词: 常染色体隐性遗传性羊毛状发, LIPH基因, 剪切突变

Abstract: Objective: To identify the pathogenic genes in two cases of autosomal recessive woolly hair with hypotrichosis (ARWH/HT). Methods: Blood samples were collected from two Chinese Han families with ARWH/HT. Next-generation genodermatosis-targeted sequencing was employed to detect gene mutations in the DNA extracted from the blood samples. Sanger sequencing was then performed for family validation, and Minigene validation was utilized to assess the pathogenicity of splicing mutations. Results: The compound heterozygous mutations of c.742C>A (p.His248Asn) and c.982+12A>G  of LIPH gene were found in proband 1, and c.629-1_629delinsTT and c.686delAinsGTAGAACCCAACCTGGCT were found in proband 2. Sanger sequencing confirmed that these compound heterozygous mutations were inherited from their mother and father, respectively. The splicing mutations c.982+12A>G and c.629-1_629delinsTT, previously unreported, were functionally characterized through Minigene validation. Conclusion: We report two novel splicing mutations in the LIPH gene and demonstrate their pathogenicity through family and Minigene validation, thereby enriching the mutation spectrum associated with ARWH/HT.

Key words: ARWH/HT, LIPH gene, splicing mutation