A novel mutation in the ATP2C1 gene is associated with Hailey-Hailey disease in a Chinese family.
BACKGROUND
A three-generation Chinese family with Hailey-Hailey disease (HHD) was identified and characterized. The proband developed HHD with severe recurrent blisters and crusted erosions involving the body folds. Skin biopsy studies showed epidermal hyperkeratosis and defects in cell-to-cell adhesion. Three other members in the family were also affected with HHD and had the same clinical manifestations. The purpose of this study was to identify the pathogenic gene or mutation in the family.


METHODS
All exons and exon-intron boundaries of ATP2C1 were polymerase chain reaction (PCR) amplified and sequenced with DNA samples from the proband. Restriction fragment length polymorphism (RFLP) analysis for the intron 23-exon 24 boundary of ATP2C1 was performed in all family members and in 100 normal control subjects.


RESULTS
A novel 2-bp deletion (c.2251delGT) was detected in exon 24 of the ATP2C1 gene. The mutation was present in the three other affected family members and in two asymptomatic young carriers, but not in the other normal family members or the 100 normal controls. The mutation resulted in a frameshift change and led to the formation of a premature termination codon (PTC) four amino acid residues downstream from the sixth transmembrane domain.


CONCLUSIONS
Our results indicate that the novel c.2251delGT (p.V751fs) mutation in the ATP2C1 gene is responsible for HHD in this Chinese family. This study expands the spectrum of ATP2C1 mutations associated with HHD.
Liu
Jiang Zhou
JZ
Key Laboratory of Molecular Biophysics of the Ministry of Education, Center for Human Genome Research, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
Liu
Zhou Jiang
ZJ
Yang
Tao
T
Li
Xiuchao
X
Liu
Mugen
M
Wang
Qing Kenneth
QK
Liu
Jing Yu
JY
D000328:Adult; D001707:Biopsy, Needle; D000252:Calcium-Transporting ATPases / Q000235:genetics*; D002681:China; D004252:DNA Mutational Analysis; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D016506:Pemphigus, Benign Familial / Q000235:genetics* / Q000473:pathology; D012150:Polymorphism, Restriction Fragment Length; D012720:Severity of Illness Index
C403624:ATP2C1 protein, human; D000252:Calcium-Transporting ATPases