Background:Acne inversa (AI),also called hidradenitis suppurativa,is a chronic,inflammatory,recurrent skin disease of the hair follicle.Familial AI shows autosomal-dominant inheritance caused by mutations in the γ-secretase genes.This study was aimed to identify the specific mutations in the y-secretase genes in two Chinese families with AI.Methods:In this study,two Chinese families with AI were investigated.All the affected individuals in the two families mainly manifested with multiple comedones,pitted scars,and a few inflammatory nodules on their face,neck,trunk,axilla,buttocks,upper arms,and thighs.Reticulate pigmentation in the flexures areas resembled Dowling-Degos disease clinically and pathologically.In addition,one of the affected individuals developed anal canal squamous cell carcinoma.Molecular mutation analysis of γ-secretase genes including PSENEN,PSEN1,and NCSTN was performed by polymerase chain reaction and direct DNA sequencing.Results:Two novel mutations ofPSENEN gene were identified,including a heterozygous missense mutation c.194T＞G (p.L65R) and a splice site mutation c.167-2A＞G.Conclusions:The identification of the two mutations could expand the spectrum of mutations in the γ-secretase genes underlying AI and provide valuable information for further study of genotype-phenotype correlations.