先天性常染色体隐性遗传性鱼鳞病一家系及PNPLA1基因突变分析  

Mutation analysis of the PNPLA1 gene in a family with autosomal recessive congenital ichthyosis

作　　者：赵惠娟[1] 闫慧敏[1] 郭独一 朱培秋 雷鹏程[1] 路雪艳[1] 姜薇[1] 

机构地区：[1]北京大学第三医院皮肤科,100191

出　　处：《中华皮肤科杂志》2017年第6期408-411,共4页Chinese Journal of Dermatology

基　　金：国家自然科学基金（81201216）

摘　　要：目的鉴定一先天性常染色体隐性遗传性鱼鳞病家系的致病基因，并探讨基因型与表型的关系。方法外周血中提取先证者及其哥、父母DNA，用全基因组外显子测序明确先证者的突变位点，根据突变位点设计特异性引物，用PCR来检测突变位点从而进一步确定该家系的致病原因。结果发现先证者PNPLA1基因的一条等位基因第4号外显子上700位的胞嘧啶C被胸腺嘧啶T替代（c．700C〉T），导致了脯氨酸变成了丝氨酸（p．pr0234ser），先证者哥也检测到相同突变；父母均为该突变基因的携带者，该突变在健康对照者中未检出。结论PNPLA1基因的错义突变（p．pr0234ser）是引起该患者临床症状的特异突变。Objective To identify a causative gene of autosomal recessive congenital ichthyosis （ARCI） in a Chinese family, and to analyze the genotype-phenotype correlation. Methods Peripheral blood samples were collected from the proband, his elder brother and parents, and genomic DNA was extracted from these blood samples. Genome- wide exome sequencing was conducted to determine the mutation site in the proband, and then allele-specific oligonueleotide primers were designed based on the mutation site. PCR was performed to detect the mutation site to further identify the causative gene of ARCI in the family. Results A new homozygous missense mutation was identified in exon 4 in 1 allele of the PNPLA1 gene in the proband, which led to a codon change from cytosine （C） to thymine （T） at position 700 （c.700C 〉 T） and resulted in the substitution of proline by serine （p.pro234ser）. The same mutation was also detected in the proband＇s brother, and his parents were the mutation carriers. No mutations were found in unrelated healthy Chinese individuals. Conclusion The missense mutation in the PNPLA1 gene （p.pro234ser） is associated with clinical symptoms of the patient with ARCI.

关 键 词：遗传性疾病 先天性 染色体障碍 突变 基因 PNPLA1 先天性常染色体隐性遗传性鱼鳞病 

分 类 号：R758.52[医药卫生—皮肤病学与性病学]