Genetic Diagnosis In A Chinese Family With Hailey-Hailey Disease

Objectives：To identify ATP2C1gene mutation in a Chinese pedigree with Hailey-Haileydisease (HHD) and perform genetic diagnosis for two young family members.Methods：Clinical data and peripheral venous blood samples from all members of the HHDfamily were obtained through field investigation. Blood samples were collected from100unrelated normal individuals in the out-patient department of Dermatology，Tongji Hospital.Genomic DNA was extracted from blood sample. All the coding exons and their flankingsequences of ATP2C1were amplified by polymerase chain reaction (PCR)，then directDNA sequencing and comparative analysis were performed.Results: There were eight members in the three-generation family. Two cases werediagnosed as HHD, both of them male. Comparative analysis to clinical features betweentwo existing patients with HHD showed that clinical symptoms of the proband were milderthan that of his son. Its genetic map verified that the disease was an autosomal dominantinheritance. A nonsense mutation, c.2416C>T(p.Arg806X), in25exon in ATP2C1wasidentified in two patients. It was not found in the healthy members of the first or secondgeneration and100unrelated control individuals. Then a genetic diagnosis was made forthe proband’s granddaughter (III1) and grandson (III2) before the clinical presentation. Last,the same mutation, c.2416C>T (p.Arg806X) in25exon in ATP2C1, was identified in III2,who was8years old.Conclusions: Our data shows that nonsense mutation c.2416C>T(p.Arg806X) in ATP2C1gene could cause HHD in Chinese Han population. III-2was discriminated by geneticdiagnosis to carry the same mutation, which means a high risk of the disease. Our findingsshould be useful to genetic counseling for the affected family.