title: Mutations in the ATP2C1 gene in Chinese patients with Hailey-Hailey disease.
abstract: Hailey-Hailey disease (HHD; MIM 16960) is a rare autosomal dominant hereditary disorder characterized by recurrent eruption of vesicles and bullae, predominantly involving the body folds. It is caused by heterozygous mutations in the ATP2C1 gene, encoding the human secretory pathway Ca2+/Mn2+-ATPase protein 1 (hSPCA1). When we studied Chinese patients with HHD, we found two different heterozygous mutations, Q506X and G353V, the former previously reported in a Hungarian patient, and the latter being a novel mutation. In a 38-year-old patient from a four-generation pedigree with a 3-year history of severe recurrent blisters, we identified a C-->T transition at nucleotide 1696, c(1696C-->T), in exon 17 of ATP2C1, resulting in a nonsenes mutation, Gln506X, which resulted in a premature termination codon. In the second patient, who represented a occurrence of sporadic Hailey-Hailey disease, a G-->T transversion of nucleotide, c(G1238T), in exon 13 of ATP2C1 was detected, which resulted in a Gly353-->Val amino acid substitution (G353V). Our molecular findings further demonstrate that the mutational events in the human ATP2C1 gene encoding the hSPCA1 pump play an important role in the pathogenesis of HHD.
authors.affiliation: Department of Dermatology, No. 1 Hospital, Wenzhou Medical College, Wenzhou, Zhejiang, China. zxq9898@yahoo.com.cn
authors.forename: X Q
authors.initials: XQ
authors.lastname: Zhang
authors.forename: H Z
authors.initials: HZ
authors.lastname: Wu
authors.forename: B X
authors.initials: BX
authors.lastname: Li
authors.forename: Y S
authors.initials: YS
authors.lastname: Xu
authors.forename: J B
authors.initials: JB
authors.lastname: Wu
authors.forename: L L
authors.initials: LL
authors.lastname: Lin
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.forename: Z M
authors.initials: ZM
authors.lastname: Li
authors.forename: X H
authors.initials: XH
authors.lastname: Lin
authors.forename: Q Y
authors.initials: QY
authors.lastname: Zhang
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D044466:Asian People; D000252:Calcium-Transporting ATPases / Q000235:genetics*; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree; D016506:Pemphigus, Benign Familial / Q000235:genetics*; D016133:Polymerase Chain Reaction
chemical_list: D018389:Codon, Nonsense; D000252:Calcium-Transporting ATPases