家族性良性天疱疮一家系报道及其ATP2C1基因筛查  

Benign familial chronic pemphigus in a family： a clinical survey and mutation analysis of ATP2C1 gene

作　　者：张学奇[1] 邵笑红[1] 蔡剑峰[1] 刘晶晶[1] 李智铭[1] 林孝华[1] 李秉煦[1] 徐云升[1] 

机构地区：[1]温州医学院附属第一医院,325000

出　　处：《中华皮肤科杂志》2013年第1期47-49,共3页Chinese Journal of Dermatology

基　　金：国家自然科学基金（30972800）

摘　　要：目的报道一个家族性良性天疱疮家系并对其致病基因ATP2C1进行突变筛查。方法对先证者及其家族4代成员进行临床调查。采集每一成员静脉血标本，同时采集50例健康人血液标本作为对照。提取外周血基因组DNA，分别对ATP2C1基因的所有28个外显子及其侧翼内含子序列进行PCR扩增，再对每一扩增产物进行直接测序，最后将测序结果分别与基因库（NM．014382．2和NC_000003．9）的编码序列和基因组序列进行逐二比对分析。结果调查该家系4代24个成员，共有8例患者。基因筛查显示先证者和该家族其他患者的ATP2C1基因第17号外显子上发生一单核苷酸碱基置换，即C（1696C→T）；同时该家族中第2代、第3代正常成员和50例健康对照均未检测到这一碱基变化。第4代4个成员中，仅有1个成员，即Ⅳ3，亦检测到这一变化。结论该家系患者ATP2C1基因发生C（1696C→T）无义突变，可能是家族性良性天疱疮的致病突变；Ⅳ3携带该突变，但到目前为止，其未发生家族性良性天疱疮的相关临床症状，有必要对其进行密切随访。Objective To report a Chinese pedigree with benign familial chronic pemphigns （BFCP）, and to screen mutations of ATP2C1 gene in this family. Methods A 39-year-old male patient with BFCP and his family members underwent a clinical investigation. Blood samples were collected from all the members in this family and from 50 unrelated healthy controls. Genomie DNA was extraeted from the blood samples, and PCR was performed to amplify all the 28 exons and flanking sequences of the ATP2C1 gene followed by DNA direct sequencing. The resulted DNA sequences were compared with the reported sequences of AFV2C1 gene in Genbank （Number：NM_014382.2 and NC_000003.9）. Results There were 24 family members in the four- generation pedigree, with 8 members affected by BFCP. A single-nucleotide substitution, c （1696C→T）, in exon 17 of the ATP2C1 gene was identified in all of the members with BFCP, but not in unaffeeted third- or second- generation members or unrelated healthy controls. This substitution was also found in 1 out of 4 family members of fourth-generation. Conclusions The nonsense mutation e（1696C→T） in the ATP2C1 gene, is likely to be responsible for BFCP in this Chinese four-generation pedigree. The underage family member of fourth- generation who carried the mutation e（1696C→T） but had no clinical symptoms of BFCP, should be closely followed.

关 键 词：家族性良性天疱疮 ATP2C1基因 家系报道 基因筛查 基因组序列 无义突变 基因组DNA 致病基因 

分 类 号：R758[医药卫生—皮肤病学与性病学]