Detection And Analysis Of ATP2C1 Gene Mutation In Patients With Familial Benign Chronic Pemphigus In Jiangxi Province

Objective:The pathogenic mutations of ATP2C1 gene in three HHD families and four sporadic patients with HHD in Jiangxi province were detected,the correlation between genotype and phenotype was analyzed,and the types and characteristics of ATP2C1 gene mutations reported worldwide were reviewed and analyzed,in order to obtain more ATP2C1 mutation information and expand the understanding of genetic counseling and gene diagnosis of HHD.Methods:1.The peripheral blood of patients with familial chronic benign pemphigus in Jiangxi Province was collected,and all exon coding regions and flanking sequences of ATP2C1 gene in HHD patients were amplified by PCR.The products were purified and Sanger sequenced,and the correlation between the detected mutation sites and the clinical manifestations of the patients was analyzed.2.The literatures about ATP2C1 gene mutation reported at domestic and abroad were searched through the databases of Pub Med and CNKI and the characteristics and types of mutations were summarized.Results:1.We detected 3 heterozygous mutations of ATP2C1 in these pedigrees and sporadic cases with HHD.Including two novel mutations(c1673＿1674ins GTTG,c.2225A>G)from two sporadic cases.Furthermore,for all three pedigrees we detected one previously reported nonsense mutation(c.1402C>T)2.According to the literature review,it is found that a total of 261 mutations of ATP2C1 gene have been recorded worldwide,including 72 missense mutations(27.59%),56 nonsense mutations(21.46%),44 splicing mutations(16.86%),75 insertion or deletion mutations(28.74%),14 duplication mutations(5.4%).Among all the mutations,there were 216 mutations in exons and 45 mutations in intron or non-coding regions.More than 50%(55.56%)of all ATP2C1 mutations may generate premature termination codons(PTCs).More than 1/3(39.85%)of ATP2C1 mutations are located in 6 exons(12,13,21,23,24 and 25).Conclusion:1.In this study,we detected the insertion mutation c1673＿1674ins GTTG and missense mutation c.2225A>G of ATP2C1 gene in two sporadic HHD patients in Jiangxi province.Through the search of the literature,it is found that these two mutations are novel mutations,which have not been reported at domestic and abroad.Our results will further expand the mutation spectrum of the ATP2C1 gene and help extend our knowledge of HHD.2.The same nonsense mutation in exon 16 was detected in three HHD families in Jiangxi Province.It is speculated that the three families may have a common genetic origin,that is,the mutation may have a founder effect in the north of Jiangxi Province,resulting in a higher incidence of the mutation in Jiangxi Province than the normal incidence.3.Literature review found that 55.56% of the ATP2C1 mutations would form PTCs,which verified the view that HHD is caused by haploinsufficiency of ATP2C1 mutants.4.Exons 12,13,21 and 25 may be the mutation hot spots of the ATP2C1 gene.