A novel NCSTN missense mutation in the signal peptide domain causes hidradenitis suppurativa, which has features characteristic of an autoinflammatory keratinization disease

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Funding sources: this work was supported by funding from the Japan Agency for Medical Research and Development JP18ek0109295h0002 and 18ek0109281h0002 to M.A. It was also supported by a Grant‐in‐Aid for Scientific Research (B) 18H02832 to M.A. and by a Grant‐in‐Aid for Young Scientists 18K16058 to T.T. from the Japan Society for the Promotion of Science.

Conflicts of interest: none to declare.

Dear Editor, NCSTN encodes nicastrin, one of the three subunits of γ‐secretase, a transmembrane endoprotease complex that catalyses the cleavage of many transmembrane proteins including Notch receptors.1 In 2010, mutations in genes encoding γ‐secretase subunits (NCSTN, PSENEN and PSEN1) were reported in patients with hidradenitis suppurativa (HS).2 Elevated tumour necrosis factor‐α and interleukin (IL)‐10 levels in patients with HS with NCSTN mutations have been found,1 although other reports found no elevation3 or found decreases.4

We investigated a three‐generation Japanese family with HS with autosomal dominant inheritance. The patient was a 42‐year‐old man with many erosions, scars, comedones and cysts on the face, neck, trunk, armpits, buttocks and extremities (Fig. 1a). A biopsy sample from the buttock showed clear evidence of hyperkeratosis of the follicular epithelium and the occlusion and dilatation of follicles by keratin plug formation (Fig. 1b, c). Interestingly, he had had severe renal failure with unknown aetiology and had received haemodialysis from his twenties.