Novel Mutations Of The ATP2C1Gene In HHD And Mutations Analysis Of The ATP2A2Gene In The Patients With DD

Benign familial chronic pemphigus（OMIM169600）,or Hailey-Haileydisease(HHD) is a uncommon autosomal dominantly inheriteddermatosis.It is characterized by suprabal separation of the epidermisresulting in recurrent blisters,crusted erosions that occur mainly on thebody folds.HHD is caused by mutations of the ATP2C1gene, whichcodes for the human secretory pathway calcium ATPcase1(Hspca1).Keratosis follicularis（OMIM124200）,or Darier’s Disease（DD) is a rareautosomal dominant hereditary skin disorder characterized by wartypapules and plaques on the seborrhoeic areas of the skin.According tosome authors, mutations in ATP2A2, a gene encodingthe sarco-endoplasmic reticulum calcium-ATPase type2isoform (SERCA2), arethe main causative factors of this pathology. Objective:1)To report twoChinese Pedigree with HHD and to the mutations in ATP2C1gene ofpatients with HHD and to investigate the still-unknow mechanism ofmolecular genetics.2)To report two Chinese Pedigree with DD and to themutations in ATP2A2gene of patients with DD and to investigate thestill-unknow mechanism of molecular genetics. Methods:1)All pedigreeinformation were collected.Skin biopsies of patients with HHD were processed for haematoxylin and eosin staining.Genomic DNA wasextracted from their peripheral blood （each patient and family memberwith HHD and100unrelated normal controls）.Polymerase chainreaction(PCR) was carried out to amplify the exons and flanking intronboundaries of theATP2C1gene followed by direct sequencing.2)Allpedigree information were collected.Skin biopsies of patients with DDwere processed for haematoxylin and eosin staining.Genomic DNA wasextracted from their peripheral blood （each patient and family memberwith HHD and100unrelated normal controls）.Polymerase chainreaction(PCR) was carried out to amplify the exons and flanking intronboundaries of the ATP2A2gene followed by direct sequencing. Results:1)Two mutations were indentified in the two unrelated families includingone splice-site mutations,one samesense mutation,one G deletionmutation:1996-1Gâ†'C mutation in exon21,1303Aâ†'G in exon13,282del G in exon3.2)Two heterozygous mutations in exon12of theATP2A2gene were indentified in the two unrelated families.Aheterozygous A to G transition occurred in nucleotide1540,which resultsin a lysine to glutamic acid substitution at codon514(K514E).Aheterozygous C to T transition at nucleotide1484,which results in aserine to leucine substitution at codon495(S495L).The missensemutation (K514E) was reported previously.No such mutation wasdetected in unaffected individuals and100unrealted controls. Conclusion:1)The two mutations(1996-1Gâ†'C,282delG) of ATP2C1gene seemed to be the reason of the Chinese families with HHD.2)Thesetwo mutations(K514E,S495L) may be the underlying causes of DD inthe two families,not common polymorphism.