一家族性良性天疱疮家系致病基因的研究

Gene Mutations in a Chinese Family with Hailey-Hailey Disease

目的为了解家族性良性天疱疮家系的基因突变方式,以及基因型与临床表型之间的关系。方法获得临床确诊患者及其家族成员外周血白细胞基因组DNA,设计针对ATP2C1基因的一系列PCR引物,运用单链构象多态性(SSCP)原理筛查此家族性良性天疱疮家系基因突变,用DNA直接测序明确具体的突变位置和方式,分析基因突变的病理意义。结果此家系存在ATP2C1基因突变,第2068-2076位“TGTAGCCAT”突变成“AGATGGAACA”,造成开放阅读框架移位,出现提前终止密码子,使其编码的蛋白质丢失了一个ATP结合位点和3个钙离子结合位点,丧失了他原有的功能而致病;此家系患者基因型与临床表型无明确关系。结论ATP2C1基因第21外显子突变是引起本家系家族性良性天疱疮的原因。

Objective To analyse gene mutation in members of a Chinese family with Hailey-Hailey disease(HHD)and study the relationship between the genotype and clinical features of the disease.Meth-ods Genomic DNA of leucocytes were obtained from members of the Chinese family with HHD including4patients and6normal persons.Ten exons of ATP2C1gene were amplified by polymerase chain reaction(PCR)and the products were analysed by single-strand conformation polymorphism(SSCP)and direct DNA sequencing.Results A novel mutation was identified in this family.The sequence of'TGTAGCCAT'(2068→2076)was substituded by'AGATGGAACA',which caused a frame shift of open reading frame and premature termination codon(PTC)in gene ATP2C1.There was no relationship between the genotypes and the phenotypes.Conclusion Gene mutation of ATP2C1gene at exon21is the cause for HHD in this fami-ly.