X-连锁隐性遗传性鱼鳞病家系的致病基因检测  

Identification of pathogenic genes of a family with X-linked ichthyosis

作　　者：王莉 娄桂予 张冰 于雪菡 秦利涛 杨科 廖世秀 WANG Li;LOU Guiyu;ZHANG Bing;YU Xuehan;QIN Litao;YANG Ke;LIAO Shixiu(Henan Key Laboratory of Genetic Diseases and Functional Genomics ,Medical Genetic Institute of Henan Provincial People's Hospital,People's Hospital of Zhengzhou University ,Zhengzhou 450003 ,China)

机构地区：[1]郑州大学人民医院河南省人民医院河南省医学遗传研究所

出　　处：《中华实用诊断与治疗杂志》2019年第7期694-696,共3页Journal of Chinese Practical Diagnosis and Therapy

基　　金：国家自然科学基金(81170581);河南省医学科技公关项目(2018020388)

摘　　要：目的分析1个X-连锁隐性遗传性鱼鳞病(X-linked ichthyosis, XLI)家系的致病基因。方法收集1个XLI家系4例患者及21例表型正常者外周血,提取基因组DNA后,采用微阵列比较基因组杂交技术检测4例患者基因组重复或缺失,采用二代测序法检测先证者基因突变情况,采用实时荧光定量PCR技术对该家系4例患者、21例表型正常者及100例健康对照组人群胎盘类固醇硫酸酯酶(placental steroid sulfatase, STS)基因可疑突变进行验证。结果微阵列比较基因组杂交技术显示XLI家系4例患者均未检测到与XLI相关的200 kb以上基因组重复或缺失;二代测序结果显示先证者STS基因第10外显子缺失突变;实时荧光定量PCR结果示4例患者STS基因第10外显子为半合子缺失突变,Ⅲ:3、Ⅲ:4、Ⅲ:8及Ⅳ:5 STS基因第10外显子为杂合缺失突变,该家系余成员及100例健康对照人群均未发现STS基因第10外显子缺失突变。结论 STS基因第10外显子缺失突变可能是该XLI家系的致病机制,二代测序联合荧光定量PCR是XLI家系致病基因诊断的准确、高效方法。Objective To explore the pathogenic gene of a family with X-linked ichthyosis(XLI). Methods The peripheral blood samples of 4 patients and 21 phenotypically normal individuals from an XLI family were collected. After extracting genomic DNA, the genomic duplications or deletion was detected by microarray comparative genomic hybridization in 4 patients. The gene mutation of the proband was detected by second-generation hybridization. The suspicious mutation of placental steroid sulfatase(STS) gene was verified by real-time fluorescence quantitative PCR in 4 patients, 21 phenotypically normal individuals and 100 healthy controls. Results The array comparative genomic hybridization showed that no genomic duplication or deletion over 200 kb related to XLI was detected in 4 patients. Exome capture sequencing showed that exon 10 of STS gene was deleted in the proband. Real-time fluorescence quantitative PCR showed that exon 10 of STS gene was a haploid deletion mutation in 4 patients, and Ⅲ:3, Ⅲ:4 and Ⅲ:8 and Ⅳ:5 in phenotypically normal individuals were heterozygous deletions. No mutation in exon 10 of STS gene was found in other members and normal controls. Conclusion The deletion mutation of exon 10 of STS gene might be the pathogenic mechanism of the XLI family. Exome capture sequencing combined with fluorescence quantitative PCR technology is an accurate and efficient method for the diagnosis of pathogenic genes in XLI family.

关 键 词：X-连锁鱼鳞病 胎盘类固醇硫酸酯酶 二代测序 

分 类 号：R758.52[医药卫生—皮肤病学与性病学] R440[医药卫生—临床医学]