Hailey-Hailey病四个家系的ATP2C1基因突变分析

Gene ATP2C1 mutation analysis for four Chinese families with Hailey-Hailey disease

目的检测Hailey-Hailey病(HHD)4个家系的致病基因ATP2C1,鉴定其突变位点和突变类型。方法采集4个HHD家系成员共9例患者和6名正常人,与100名无关健康对照者外周静脉血各2 ml,提取全基因组DNA。运用聚合酶链反应(PCR)扩增ATP2C1基因的全部28个外显子及其侧翼内含子序列,扩增产物纯化后进行DNA直接测序,BLAST比对分析其突变位点和突变方式。结果在9例HHD患者中共检出了3个ATP2C1基因致病突变:c.888_889ins T(p.296Tfs X2)、c.1330del C(p.443Qfs X33)和c.2416C>T(p.Arg806X)。在4个HHD家系的6名正常者和100名健康对照者中均未发现上述突变。结论在9个HHD家系患者中存在2个移码突变(c.888_889ins T和c.1330del C)及1个无义突变(c.2416C>T),其中2个移码突变为首次报道。这些突变的发现有助于HHD的诊断,并丰富了HHD相关ATP2C1突变数据库。

Objective To identify ATP2C1 gene mutations in four Chinese families with Hailey-Hailey disease（HHD）. Methods Genomic DNA was extracted from peripheral blood of 9 patients and 6 healthy individuals of 4 HHD families and 100 unrelated normal individuals. All 28 coding exons and their fl anking sequences of ATP2C1 were amplifi ed by polymerase chain reaction（PCR）, then direct DNA sequencing and comparative analysis were performed. Results Three ATP2C1 gene heterozygous mutations, c.888_889ins T（p.296 TfsX2）, c.1330 del C（p.443 QfsX33） and c.2416C〉T（p.Arg806X）, were identifi ed in 9 patients with HHD. The mutations were not found in the healthy members of the 4 families and normal controls. Conclusion Two novel heterozygous mutations of ATP2C1 gene, c.888_889ins T（p.296 TfsX2） and c.1330 del C（p.443 QfsX33）, were found among these HHD cases in this study. Our fi ndings provided data for molecular diagnosis of these HHD patients, and added new variants to the database of ATP2C1 mutations associated with HHD.