中华皮肤科杂志 ›› 2018, Vol. 51 ›› Issue (10): 737-740.doi: 10.3760/cma.j.issn.0412-4030.2018.10.007

• 论著 • 上一篇    下一篇

先天性常染色体隐性遗传性鱼鳞病两家系ABCA12基因突变分析

刘婷婷,杨发灯,林志淼,汪慧君,胡凌寒,钟伟龙,杨勇   

  1. 100034北京大学第一医院皮肤科
  • 收稿日期:2018-01-10 修回日期:2018-07-03 出版日期:2018-10-15 发布日期:2018-10-03
  • 通讯作者: 杨勇 E-mail:dryongyang@bjmu.edu.cn
  • 基金资助:
    国家杰出青年科学基金(81425020)

Mutation analysis of the ABCA12 gene in two families with autosomal recessive congenital ichthyosis

Liu Tingting, Yang Fadeng, Lin Zhimiao, Wang Huijun, Hu Linghan, Zhong Weilong, Yang Yong   

  1. Department of Dermatology, Peking University First Hospital, Beijing 100034, China
  • Received:2018-01-10 Revised:2018-07-03 Online:2018-10-15 Published:2018-10-03
  • Contact: Yang Yong E-mail:dryongyang@bjmu.edu.cn
  • Supported by:
    National Science Foundation for Distinguished Young Scholars(81425020)

摘要: 目的 检测两个先天性常染色体隐性遗传性鱼鳞病家系ABCA12基因的突变情况。方法 根据典型的临床表现,2例先证者确诊为先天性常染色体隐性遗传性鱼鳞病。提取患者及其父母的外周血DNA,使用遗传性皮肤病多基因芯片对先证者进行高通量测序,确定突变位点,再用Sanger测序法对先证者和父母的DNA进行双向验证。结果 例1发现ABCA12基因上c.2759A>G和c.7004A>G两个复合杂合突变;例2发现ABCA12基因上c.6163_6164insT和c.7406G>A两个复合杂合突变。2例患者的父母均是其中1个突变的携带者。对这4个突变进行功能预测显示,c.2759A>G、c.7004A>G和c.7406G>A三个错义突变均有可能的致病作用,另外移码突变c.6163_6164insT编码的截断蛋白也可能影响蛋白质功能。c.2759A>G、c.6163_6164insT为新发现的突变位点。结论 ABCA12基因复合杂合突变是两个家系先证者的致病突变。

关键词: 鳞癣, DNA突变分析, 高通量核苷酸序列分析, 先天性常染色体隐性遗传性鱼鳞病, ABCA12基因, 遗传性皮肤病多基因芯片, 复合杂合突变

Abstract: Objective To detect mutations of the ABCA12 gene in 2 Chinese families with autosomal recessive congenital ichthyosis (ARCI). Methods According to the typical clinical manifestations, two probands were diagnosed with ARCI. DNA was extracted from the peripheral blood samples collected from the patients and their parents. High-throughput sequencing was conducted by using multi-gene array for genetic skin disorders to determine mutation sites in the probands, and then DNA isolated from the probands and their parents were bidirectionally verified by Sanger sequencing. Results Two compound heterozygous mutations (c.2759A>G and c.7004A>G) in the ABCA12 gene were found in the proband 1, and another two compound heterozygous mutations (c.6163_6164insT and c.7406G>A) were identified in the proband 2. The parents of the two probands were heterozygous carriers of one of the two mutations in the ABCA12 gene. Function prediction for the 4 mutations showed that all of the 3 missense mutations (c.2759A>G, c.7004A>G and c.7406G>A) may exert pathogenic effect, and fragmin encoded by the frameshift mutation c.6163_6164insT may also affect protein function. c.2759A>G and c.6163_6164insT were newly identified mutation sites. Conclusion The compound heterozygous mutations in the ABCA12 gene are the causative mutations responsible for ARCI in the two probands of the two pedigrees.

Key words: Ichthyosis, DNA mutational analysis, High?throughput nucleotide sequencing, Autosomal recessive congenital ichthyosis, ABCA12 gene, Multi?gene array for genetic dermatology, Compound heterozygous mutation

中图分类号: 

  • R75