Zhang X Q, Wu H Z, Li B X, Xu Y S, Wu J B, Lin L L, Yang Y, Li Z M, Lin X H, Zhang Q Y
Department of Dermatology, No. 1 Hospital, Wenzhou Medical College, Wenzhou, Zhejiang, China.
Clin Exp Dermatol. 2006 Sep;31(5):702-5. doi: 10.1111/j.1365-2230.2006.02204.x.
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.
黑利-黑利病（HHD；MIM 16960）是一种罕见的常染色体显性遗传性疾病，其特征为水疱和大疱反复发疹，主要累及身体褶皱部位。它由ATP2C1基因突变所致，该基因编码人类分泌途径Ca2+/Mn2+-ATP酶蛋白1（hSPCA1）。在我们对中国HHD患者的研究中，发现了两种不同的杂合突变，即Q506X和G353V，前者先前在一名匈牙利患者中报道过，后者是一种新突变。在一名来自四代家系、有3年严重反复水疱病史的38岁患者中，我们在ATP2C1基因第17外显子中鉴定出核苷酸1696处的C→T转换，即c(1696C→T)，导致无义突变Gln506X，产生了一个提前终止密码子。在第二名代表散发性黑利-黑利病病例的患者中，检测到ATP2C1基因第13外显子中核苷酸的G→T颠换，即c(G1238T)，导致甘氨酸353→缬氨酸的氨基酸替代（G353V）。我们的分子研究结果进一步证明，编码hSPCA1泵的人类ATP2C1基因中的突变事件在HHD的发病机制中起重要作用。
