A novel splice site mutation in NCSTN underlies a Japanese family with hidradenitis suppurativa

Background Hidradenitis suppurativa (HS) is a chronic follicular occlusive disease with characteristic recurrent draining sinuses, skin abscesses and disfiguring scars, mainly involving the axilla, groin, perianal and perineal regions. While most HS cases are nonfamilial, familial cases showing autosomal dominant inheritance have been reported. Recently, loss-of-function mutations in the genes encoding gamma-secretase have been identified as a cause of familial HS in the Chinese and British populations. Objectives To identify mutations in the genes encoding gamma-secretase in Japanese patients with familial and nonfamilial HS. Methods Two affected and three unaffected individuals from a Japanese family with familial HS and nine patients with nonfamilial HS were recruited. We conducted mutation analysis of the gamma-secretase genes in Japanese patients with familial and nonfamilial HS. Results A novel splice site mutation in the nicastrin gene NCSTN, one of the six key component genes encoding gamma-secretase, was identified in the patients with familial HS. Neither unaffected individuals in the family nor 100 ethnically matched control alleles carry this mutation. None of the nine patients with nonfamilial HS carry nonsense, frameshift or splice site mutations in this gene. Conclusions A novel splice site mutation, c.582+1delG, in NCSTN was identified in the familial patients with HS. We also reveal for the first time that a gamma-secretase gene mutation is not linked to the development of nonfamilial HS. These results would further pave the way to a better understanding of the contribution of gamma-secretase and other genes to the pathogenesis of HS and to the development of a new therapeutic strategy for HS.