Identification Of One Novel Mutation Of The NCSTN Gene In One Chinese Acne Inversa Family

Background: Acne inversa (AI; also known as hidradenitis suppurativa and thefollicular occlusion triad; OMIM142690), which is characterized by chronic,inflammatory, recurrent, debilitating, skin follicular disease that usually presents afterpuberty with painful deep seated, inflamed lesions in the apocrine gland-bearing areaof the body, most commonly, the axillary, inguinal and anogenital regions. AI usuallyshows an autosomal dominant inheritance pattern and appears to be geneticallyheterogeneous. γ-Secretase is a transmembrane protease consisting of four essentialprotein subunits: one catalytic presenilin subunit and three cofactor subunits,encodedby PSEN1、PSENEN、NCSTN、APH1. It mediates intramembranous cleavage ofvarious type I membrane proteins, including amyloid precursor protein and Notch. Upto date,21mutations in17AI families and4AI sporadic individuals have beenidentified in the three gene PSEN1、PSENEN、NCSTN(one located in PSEN1,threelocated in PSENEN,17located in NCSTN). Two AI autosomal dominant multiplexkindreds families were recruited in our study. Direct sequencing was performed in Allcoding exons including intron–exon boundaries of NCSTN (17exons), PSEN1(10exons), and PSENEN (3exons).Objective: Here, genetic investigation of. two AI autosomal dominant multiplexkindreds families were performed by us.Methods: Polymerase chain reaction(PCR) and direct sequencing of the threegene PSEN1、PSENEN、NCSTN were performed to identify and confirm the mutations in the patients.Results: One novel mutation c.497C>A (p. S166X) mutation in the exon5ofNCSTN gene was identified in family1. And it was not observed in the unaffectedfamily members and100unrelated controls. While in family2, we failed to observeany mutation in the coding regions of the three above genes (NCSTN, PSEN1,PSENEN). Only one novel SNP c.837+16G>T in intron8of the PSEN1gene wasdetected in the two families as well as two healthy controls. This SNP has not beenreported in the NCBI Single-Nucleotide Polymorphism Database.Conclusion: A heterozygous nonsense c.497C>A (p. S166X) mutation in theexon5of NCSTN gene was identified in family1. This mutation was first identified inAcne inversa which expanded the gene database of AI and should be useful for theunderstanding of the pathogenesis of AI. We failed to identify any mutation in family2,indicating the strong genetic heterogeneity of AI.