Two novel ATP2C1 mutations in patients with Hailey-Hailey disease and a literature review of sequence variants reported in the Chinese population

Genet Mol Res. 2015 Dec 29;14(4):19349-59. doi: 10.4238/2015.December.29.45.

Abstract

Hailey-Hailey disease (HHD) is an autosomal dominant disorder in which the ATP2C1 gene has been implicated. Many mutations of this gene have been detected in HHD patients. To analyze such mutations in HHD and summarize all those identified in Chinese patients with this disease, we examined four familial and two sporadic cases and searched for case reports and papers by using the Chinese Biological Medicine Database and PubMed. HHD diagnoses were made based on clinical features and histopathological findings. Polymerase chain reaction and direct sequencing of the ATP2C1 gene were performed using blood samples from HHD patients, unaffected family members, and 120 healthy individuals. Three mutations were identified, including the recurrent mutation c.2126C>T (p.Thr709Met), and two novel missense mutations, c.2235_2236insC (p.Pro745fs*756) and c.689G>A (p.Gly230Asp). Considering our data, 81 different mutations have now been reported in Chinese patients with HHD. In cases of misannotation or duplication, previously published mutations were renamed according to a complementary DNA reference sequence. These mutations are scattered throughout the ATP2C1 gene, with no evident hotspots or clustering. It is of note that some reported "novel" mutations were in fact found to be recurrent. Our findings expand the range of known ATP2C1 sequence variants in this disease.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Asian People
  • Base Sequence
  • Calcium-Transporting ATPases / genetics*
  • Case-Control Studies
  • Child
  • Female
  • Gene Expression
  • Genes, Dominant
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation*
  • Pedigree
  • Pemphigus, Benign Familial / diagnosis
  • Pemphigus, Benign Familial / ethnology
  • Pemphigus, Benign Familial / genetics*
  • Pemphigus, Benign Familial / pathology
  • Sequence Analysis, DNA
  • Terminology as Topic

Substances

  • ATP2C1 protein, human
  • Calcium-Transporting ATPases