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S. Duchatelet, S. Miskinyte, O. Join‐Lambert, M.‐N. Ungeheuer, C. Francès, A. Nassif, A. Hovnanian, First nicastrin mutation in PASH (pyoderma gangrenosum, acne and suppurative hidradenitis) syndrome, British Journal of Dermatology, Volume 173, Issue 2, 1 August 2015, Pages 610–612, https://doi.org/10.1111/bjd.13668
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Funding sources: This work was supported by Fondation pour la Recherche Médicale (ROXANNE project, LMV20100519581).
Conflicts of interest: none declared.
Dear Editor, PASH (pyoderma gangrenosum, acne and suppurative hidradenitis) syndrome is a new clinical entity associating pyoderma gangrenosum (PG), severe acne and hidradenitis suppurativa (HS).1 The absence of pyogenic sterile arthritis (PA) distinguishes PASH syndrome from PAPASH (pyogenic arthritis, pyoderma gangrenosum, acne and hidradenitis suppurativa) and PAPA (pyogenic arthritis, pyoderma gangrenosum and acne) syndromes, which exhibit PA in combination with PG, severe acne with or without HS, respectively.2 3 Mutations in the coding region of the proline‐serine‐threonine‐phosphatase interacting protein 1 gene (PSTPIP1) were identified in patients with PAPA and PAPASH syndromes, although PAPA syndrome is genetically heterogenous.2 3 HS (OMIM#142690) is a chronic skin disease characterized by nodules, cysts and abscesses in apocrine gland‐bearing sites. Loss‐of‐function mutations in the γ‐secretase genes, nicastrin (NCSTN), presenilin enhancer gamma secretase subunit (PSENEN) and presenilin 1 (PSEN1), have been reported in a small number of HS cases.4 5 Furthermore, γ‐secretase is an intramembranous protease complex capable of cleaving transmembrane proteins, including Notch receptors.6 Mutations in the γ‐secretase genes may impair Notch signalling, which plays a crucial role in epidermal homeostasis.5 7