一个毛囊角化症家系的ATP2A2基因突变分析  

Detection and analysis of an ATP2A2 mutation in a family with Darier-White disease

作　　者：陈熙慧 刘清波[1] 孙茂[1] 袁利娟 吴元明[1] Chen Xihui;Liu Qingbo;Sun Mao;Yuan Lijuan;Wu Yuanming(Department of Biochemistry and Molecular Biology, Center for DNA Typing, the Fourth Military Medical University, Xi’an,Shaanxi 710032, China;Department of General Surgery,Tangdu Hospital,the Fourth Military Medical University, Xi’an,Shaanxi 710038,China)

机构地区：[1]第四军医大学分子生物学与生物化学教研室、DNA分型中心,西安710032 [2]第四军医大学唐都医院普通外科,西安710038

出　　处：《中华医学遗传学杂志》2019年第8期794-797,共4页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金(81671476,81502424);陕西省重点产业创新项目(2016KTZDSF-01-03).

摘　　要：目的探讨1例毛囊角化症家系的分子发病机制。方法提取该家系3例患者、1名正常成员以及80名正常对照的基因组DNA,结合目标序列捕获和高通量测序从皮肤病相关的基因中筛选出候选突变,应用Sanger测序和家系共分离分析进行验证。通过保守性分析、蛋白质结构及功能预测分析其致病性。结果3例患者ATP2A2基因的第15外显子均存在c.2246G>T(p.G749V)杂合突变,在1名正常成员以及80名正常对照中未发现上述突变。该位点的氨基酸在进化中高度保守,其突变将改变蛋白质的结构和功能。结论ATP2A2 c.2246G>T为该毛囊角化症家系的致病突变,可能通过破坏肌浆/内质网钙离子ATP酶2原有的结构和功能而致病。Objective To explore the molecular basis for a pedigree affected with Darier-White disease. Methods Genomic DNA was isolated from 3 patients and 1 unaffected member from the pedigree, as well as 80 healthy controls. Targeted sequence capture and next-generation sequencing were used to screen mutations of skin disease-related genes. Candidate mutations were verified by Sanger sequencing, and co-segregation analysis was carried out to confirm the pathogenicity of mutation. Conservation analysis and protein structure and function were also predicted with Bioinformatic tools. Results A heterozygous mutation c. 2246G>T (p.G749V) was identified in exon 15 of ATP2A2 gene in all 3 patients from the pedigree, but not in the unaffected member or 80 healthy controls. The corresponding amino acid was highly conserved, and mutation of which can lead to structural and functional changes of the protein. Conclusion The c. 2246G>T missense mutation of the ATP2A2 gene probably underlies the Darier-White disease in this pedigree by causing damages to the structure and function of sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2).

关 键 词：目标序列捕获 高通量测序 毛囊角化症 ATP2A2基因 肌浆/内质网钙离子ATP酶2 

分 类 号：R758[医药卫生—皮肤病学与性病学]