Deficiency of the Human Cysteine Protease Inhibitor Cystatin M/E Causes Hypotrichosis and Dry Skin

July 2019 in “ Genetics in medicine ”

Ellen H.J. van den Bogaard, Michel van Geel, Ivonne M.J.J. van Vlijmen-Willems, Patrick A. Jansen, Malou Peppelman, P.E.J. van Erp, Selma Atalay, Hanka Venselaar, Marleen Simon, Marieke Joosten, Joost Schalkwijk, Patrick L.J.M. Zeeuwen

cystatin M/E CST6 gene hypotrichosis eczema blepharitis photophobia impaired sweating legumain cathepsins L cathepsins V epidermal homeostasis hair follicle development dry skin hair loss

TLDR Lack of cystatin M/E causes thin hair and dry skin.

The study investigated the role of the cysteine protease inhibitor cystatin M/E, encoded by the CST6 gene, in hair and skin diseases. Genetic analysis of two related patients with hypotrichosis revealed a homozygous c.361C>T (p.Gln121*) variant in CST6, leading to a premature stop codon. This mutation was associated with symptoms like hypotrichosis, eczema, blepharitis, photophobia, and impaired sweating. Functional assays showed that the mutant cystatin M/E could not inhibit its target proteases (legumain and cathepsins L and V). The findings highlighted the critical role of cystatin M/E in maintaining epidermal homeostasis and hair follicle development.

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