A novel NCSTN gene mutation in a Chinese family with acne inversa.

Acne inversa (AI) is a chronic inflammatory disease of hair follicles. The pathogenesis of AI remains unclear. Haploinsufficiency of genes encoding γ-secretase components is the genetic basis for a subset of familial AI. Idiopathic guttate hypomelanosis (IGH) is a leukoderma characterized by multiple porcelain-white macules. Familial AI associated with IGH has not been reported previously. Herein, we present the pathogenic variation in a Chinese Han family with AI and IGH. Peripheral blood samples were collected from 16 members of the entire family. Eighteen exons and flanking introns of the NCSTN gene were amplified by polymerase chain reaction. Two hundred unrelated healthy Chinese subjects were used as controls. Sequencing results were analysed using CodonCode Aligner Software. Seven of the 16 family members in three generations were AI patients. Six AI patients also had IGH, while the other only had AI. One had IGH without AI. All AI patients carried the mutation, c.218delC, located in exon 4 of NCSTN. The deletion mutation led to a reading frame shift and the appearance of a premature termination codon (p.P73Lfs*15), resulting in the production of truncated protein. Family members without AI did not carry this mutation, indicating that it cosegregated with the phenotype. The mutation was not detected among the controls. This mutation has not been reported in the EXaC, HGMD, and dbSNP databases. In addition, we performed whole-exome sequencing on the proband and finally screened six candidate genes, ADAMTS2, BUB1B, CRB2, FBLN1, SEC24B, and WNK1, which we further validated in effected family members, and none of them were cosegregated. In conclusion, we identified a novel deletion mutation in exon 4 of NCSTN, which may underlie the molecular pathogenesis in this AI family. However, we found no relationship between this mutation and IGH.