Deficiency of the human cysteine protease inhibitor cystatin M/E causes hypotrichosis and dry skin.

ABSTRACT:

Purpose

We aimed to assess the biological and clinical significance of the human cysteine protease inhibitor cystatin M/E, encoded by the CTS6 gene, in diseases of human hair and skin.

Methods

Exome and Sanger sequencing was performed to reveal the genetic cause in two related patients with hypotrichosis. Immunohistochemical, biophysical, and biochemical measurements were performed on patient skin and 3D-reconstructed skin from patient-derived keratinocytes.

Results

We identified a homozygous variant c.361C>T (p.Gln121*), resulting in a premature stop codon in exon 2 of CST6 associated with hypotrichosis, eczema, blepharitis, photophobia and impaired sweating. Enzyme assays using recombinant mutant cystatin M/E protein, generated by site-directed mutagenesis, revealed

SUBMITTER: van den Bogaard EHJ 

PROVIDER: S-EPMC6752276 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature