一婴儿期发病的慢性家族性良性天疱疮家系ATP2C1基因突变研究

Mutation analysis of ATP2C1 gene in a Chinese pedigree with infancy-onset Hailey-Hailey disease （HHD）

目的对一慢性家族性良性天疱疮家系进行测序，寻找ATP2C1基因外显子上的突变点，丰富关于ATP2C1基因突变的信息。方法提取一慢性家族性良性天疱疮家系中先证者及包括其父母、舅舅在内的家族中6名其他成员的外周血DNA进行测序，与人类基因组ATP2C1序列相比较找出突变点，另外涣050例正常人血的ATP2C1基因，除外单核苷酸多态性。结果家系中先证者、其舅舅及其母亲在ATP2C1的第9外显子上存在一杂合性的剪切突变，第699位缺失腺嘌呤（A），导致其下游第12位的氨基酸序列出现终止密码TGA。反向测序亦证实该突变。该家系中先证者父亲、其他3名成员及50例正常人均未见该突变。结论本研究慢性家族性良性天疱疮家系中先证者及其母亲及舅舅ATP2C1的第9外显子上存在一杂合性的剪切突变，突变来自于母系并向下遗传。

Objective To analyse the mutation of ATP2C1 gene in a Chinese pedigree with iniancy- onset HHD. Methods Blood samples were collected from the proband, his affected uncle, 4 unaffected family members, and 50 unrelated normal controls. DNA was extracted and PCR was performed to amplify all the 27 exons and flanking sequences of ATP2C1 gene followed by DNA sequencing. Results A heterozygous splicing mutation, c.699delA, which resulted in a premature termination mutation （PTC） in exon 9 at amino acid 12, was identified in the ATP2C1 gene of the proband, his uncle and mother. Reverse DNA sequencing confirmed the mutation, which was absent in 4 other family members and 50 normal controls. Conclusion A heterozygous splicing mutation, which may be maternally inherited, is detected in exon 9 of ATP2C1 gene in the proband, his mother and uncle.