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.
KeywordsAcne inversa Idiopathic guttate hypomelanosis Nicastrin Deletion mutation
This present study was supported by CAMS Initiative for Innovative Medicine (Grant no. 2017-I2M-B&R-01) and CAMS Innovation Fund for Medical Sciences (Grant no. 2016-I2M-1-002).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Informed consent was obtained from all individual participants included in the study.
- Kim JY, Kang HY, Lee ES, Kim YC (2005) Addison’s disease with idiopathic guttate hypomelanosis. Korean J Dermatol 43:1419–1422Google Scholar
- Liu Y, Gao M, Lv YM, Yang X, Ren YQ, Jiang T, Zhang X, Guo BR, Li M, Zhang Q, Zhang P, Zhou FS, Chen G, Yin XY, Zuo XB, Sun LD, Zheng XD, Zhang SM, Liu JJ, Zhou Y, Li YR, Wang J, Wang J, Yang HM, Yang S, Li RQ, Zhang XJ (2011) Confirmation by exome sequencing of the pathogenic role of NCSTN mutations in acne inversa (hidradenitis suppurativa). J Investig Dermatol 131:1570–1572CrossRefGoogle Scholar
- Ratnamala U, Jhala D, Jain NK, Saiyed NM, Raveendrababu M, Rao MV, Mehta TY, Al-Ali FM, Raval K, Nair S, Chandramohan NK, Kuracha MR, Nath SK, Radhakrishna U (2016) Expanding the spectrum of gamma-secretase gene mutation-associated phenotypes: two novel mutations segregating with familial hidradenitis suppurativa (acne inversa) and acne conglobata. Exp Dermatol 25:314–316CrossRefGoogle Scholar