Differential Profiles of Gamma-Secretase-Notch Signaling in Hidradenitis Suppurativa: The Need for Genotype-Endotype-Phenotype Analysis.

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Hidradenitis Suppurativa (HS) is a chronic inflammatory dermatosis in which a subset of patients display genetic variants in components of the gamma secretase complex1 proposed to result in dysregulation of Notch signaling2 . This pathogenic paradigm has been highly influential in providing a succinct explanation for the pathogenesis of HS, however the molecular data supporting the hypothesis has been relatively sparse, and largely derived from East Asian populations3,4 . The incidence of Gamma-Secretase associated polymorphisms been demonstrated to be significantly lower in Caucasian populations5 , implying that other unknown genetic contributors to HS exist in Caucasian populations.


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