title: A novel splice site mutation in NCSTN underlies a Japanese family with hidradenitis suppurativa.
abstract: 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 γ-secretase have been identified as a cause of familial HS in the Chinese and British populations.
  
  
  OBJECTIVE
  To identify mutations in the genes encoding γ-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 γ-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 γ-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 γ-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 γ-secretase and other genes to the pathogenesis of HS and to the development of a new therapeutic strategy for HS.
authors: Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors: Y
authors: Y
authors: Nomura
authors: T
authors: T
authors: Nomura
authors: K
authors: K
authors: Sakai
authors: K
authors: K
authors: Sasaki
authors: Y
authors: Y
authors: Ohguchi
authors: O
authors: O
authors: Mizuno
authors: H
authors: H
authors: Hata
authors: S
authors: S
authors: Aoyagi
authors: R
authors: R
authors: Abe
authors: Y
authors: Y
authors: Itaya
authors: M
authors: M
authors: Akiyama
authors: H
authors: H
authors: Shimizu
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D006579:Heterozygote; D017497:Hidradenitis Suppurativa / Q000235:genetics*; D006801:Humans; D007564:Japan; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D022821:RNA Splice Sites / Q000235:genetics*
chemical_list: D008562:Membrane Glycoproteins; D022821:RNA Splice Sites; C413604:nicastrin protein; D053829:Amyloid Precursor Protein Secretases