Deficiency of the Human Cysteine Protease Inhibitor Cystatin M/E Causes Hypotrichosis and Dry Skin
September 2019
in “
The journal of investigative dermatology/Journal of investigative dermatology
”
cystatin M/E hypotrichosis CST6 gene eczema blepharitis acanthosis collagen fiber density epidermal differentiation genes legumain cathepsins L cathepsins V epidermal homeostasis hair follicle morphogenesis autosomal recessive hypotrichosis syndrome dry skin reduced hair growth skin biopsy cell proliferation
TLDR Not having enough cystatin M/E protein causes less hair growth and dry skin.
The study investigated the role of the human cysteine protease inhibitor cystatin M/E in hair and skin diseases by examining two related patients with hypotrichosis, a condition characterized by reduced hair growth. The researchers identified a homozygous mutation c.361C>T (p.Gln121*) in the CST6 gene, which led to a premature stop codon and resulted in various symptoms including eczema, blepharitis, photophobia, and impaired sweating. Skin biopsies showed acanthosis and abnormal collagen fiber density, while immunostainings indicated increased cell proliferation and upregulated expression of epidermal differentiation genes. The mutant cystatin M/E protein was unable to inhibit its target proteases, legumain, cathepsins L, and V, due to disturbed protease/inhibitor binding sites confirmed by 3D-protein structure prediction. These findings suggest that cystatin M/E plays a crucial role in epidermal homeostasis and hair follicle morphogenesis, and its deficiency leads to the described autosomal recessive hypotrichosis syndrome.
