Detection and comparison of two types of ATP2C1 gene mutations in Chinese patients with Hailey-Hailey disease

The gene ATP2C1 is identified as the defective gene in Hailey-Hailey disease (HHD). The nonsense and missense are two common types of mutations and have ,respectively, been detected in many HHD patients. The aims of our study were to identify the pathogenic ATP2C1 abnormality in Chinese HHD patients, and to compare nonsense and missense mutations in vivo to provide further understanding of the molecular and the physiological basis of HHD. The nucleotide sequencing of the ATP2C1 gene was performed in HHD patients, unaffected family mem- bers and 100 unrelated individuals. Meanwhile, we detec- ted and analyzed the clinical manifestations, the expression of ATP2C1 mRNA and hSPCA1 protein in the two types of mutations. Three heterozygous mutations were identified, including a previously reported nonsense mutation (R799X), two novel missense mutations (D644G) and (R417K). The results of comparisons between two types of mutations showed that the common clinical features, the similarly low-level expressions of ATP2C1 mRNA and hSPCA1 protein, but the ATP2C1 mRNA expression of nonsense mutation was lower than missense mutation and even less than half the level of normal people. Our findings expand the known spectrum of ATP2C1 mutations in HHD. We supported the haploinsufficiency theory as pre- valent mechanism in both types of mutations, and believed that the differences of ATP2C1 mRNA expressions in peripheral blood may relate with the type of mutation and reflect the state of illness of patients.