Gamma-secretase gene mutations in familial acne inversa

Science. 2010 Nov 19;330(6007):1065. doi: 10.1126/science.1196284. Epub 2010 Oct 7.


Acne inversa (AI), also known as hidradenitis suppurativa, is a chronic, recurrent, inflammatory disease of hair follicles that often runs in families. We studied six Chinese families with features of AI as well as additional skin lesions on back, face, nape, and waist and found independent loss-of-function mutations in PSENEN, PSEN1, or NCSTN, the genes encoding essential components of the γ-secretase multiprotein complex. Our results identify the γ-secretase component genes as the culprits for a subset of familial AI, implicate the γ-secretase-Notch pathway in the molecular pathogenesis of AI, and demonstrate that familial AI can be an allelic disorder of early-onset familial Alzheimer's disease.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Alzheimer Disease / genetics
  • Amyloid Precursor Protein Secretases / genetics*
  • Asian People / genetics
  • Chromosomes, Human, Pair 19
  • DNA Mutational Analysis
  • Female
  • Hidradenitis Suppurativa / enzymology*
  • Hidradenitis Suppurativa / genetics*
  • Humans
  • Male
  • Membrane Glycoproteins / genetics
  • Membrane Proteins / genetics
  • Middle Aged
  • Mutation*
  • Presenilin-1 / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Young Adult


  • Membrane Glycoproteins
  • Membrane Proteins
  • PSEN1 protein, human
  • PSENEN protein, human
  • Presenilin-1
  • nicastrin protein
  • Amyloid Precursor Protein Secretases