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Autosomal recessive exfoliative ichthyosis (AREI) results from biallelic loss-of-function variants in CSTA. We report a 25-year-old man born to consanguineous parents who presented with congenital erythroderma, hyperhidrosis and diffuse hyperkeratosis; genetic analysis identified a novel homozygous c.172C>T (p.Arg58Ter) variant in CSTA, consistent with AREI ([PMID:25400170]). Immunostaining showed absence of epidermal cystatin A, and electron microscopy demonstrated reduced cornified envelope thickness and disturbed lamellar lipid bilayers with delayed lamellar body processing, confirming epidermal barrier abnormalities ([PMID:25400170]).
This single proband report provides limited genetic evidence, but concordant functional data support a pathogenic role for CSTA loss-of-function in AREI.
Gene–Disease AssociationLimitedSingle consanguineous proband with homozygous loss-of-function variant and concordant experimental evidence Genetic EvidenceLimitedOne homozygous LoF variant identified in one individual without further segregation ([PMID:25400170]) Functional EvidenceModerateImmunostaining showed absence of cystatin A and ultrastructural analyses demonstrated epidermal barrier abnormalities ([PMID:25400170]) |