Analysis On Mutations Of ATP2C1 Gene In Patients With Familial Chronic Benign Pemphigus

Background Familial chronic benign pemphigus(OMIM 169600)is a clinically rare autosomal dominant hereditary skin disease first reported by the Hailey brothers in 1939,also known as Hailey-Hailey disease(HHD).Patients often present with erythema,blisters,bullae,erosion,etc.in the folds of the armpits,under the breasts,groin,and perianal area.The rash often appears repeatedly.There may be bad odor when accompanied by infection.The histopathological feature is that the acanthus layer on the basal cell layer in the epidermis is loosened,forming epidermal fissures and blisters,and some of them have a collapsed brick-like appearance.Some scholars have found that the occurrence of this disease is related to the ATP2C1 gene mutation,which encodes the Golgi human secretory pathway Ca2+/Mn2+-ATPase protein 1(h SPCA1).With the extensive research on familial chronic benign pemphigus by domestic and foreign scholars,more than 180 ATP2C1 gene mutations have been reported,including missense mutations,nonsense mutations,insertion or deletion mutations,and cleavage site mutations.Most of these mutations led to the formation of premature terminal codon(PTC),resulting in loss of structure and function of the encoded protein.The single dose deficiency caused by the pathogenic mutation of ATP2C1 gene is the main mechanism of HHD dominant inheritance.At the same time,similar ratio mutation sites were found in exon2 to exon27,so the hot spot mutation was not clear.Some studies have also found that exon22 may be a specific mutation region of Asian species.Aim To detection of mutation sites in familial chronic benign pemphigus,and summary of mutation types and mutation characteristics of ATP2C1 gene reported by scholars at domestic and foreign.Methods Sanger sequencing was used to detect the mutations of ATP2C1 gene in two HHD families and two sporadic cases.The sequencing results were analyzed by Chromas2.0 software.The previous reports of HHD mutations were summarized and analyzed.Results 1.A missense mutation c.920 C > T(p.P307L)was found in two families and one sporadic case.Literature review found that 187 pathological mutations have been reported so far(27.27% of them are missense mutations,15.51% are Nonsense mutations,19.25% are Splice mutation,37.97 % are insertion or deletion mutations).2.There are 151 mutations were found in exons(14 mutations were reported in exon 12 and 13,13 mutations were found in exon 17,21,and 23),and 36 mutations in intron or non-coding regions.Conclusions 1.The missense mutation of exon 12 of ATP2C1 gene c.920 C > T(p.P307L),once reported by Chinese scholars,has not been reported in foreign HHD patients,and the two families of this study and The mutation was detected in a sporadic case,which may be one of the hotspot mutations in Chinese HHD patients.2.Literature review found that the ATP2C1 gene mutation type is mainly deletion and insertion mutation.3.Exons 12,13,17,21 and 23 may be the mutation hotspot region.