Recessive progressive symmetric erythrokeratoderma results from a homozygous loss-of-function mutation ofKRT83and is allelic with dominant monilethrix

Abstract

At least some cases of PSEK result from loss-of-function mutations in . Heterozygous missense substitutions in have been implicated in autosomal dominant monilethrix, a rare hair disorder. Our findings indicate that at least some cases of autosomal recessive PSEK and autosomal dominant monilethrix are allelic, respectively resulting from loss-of-function and missense mutations in the gene. Together, these findings indicate that different types of mutations in can result in quite different skin and hair phenotypes.

Gain-of-Function Mutations in TRPM4 Activation Gate Cause Progressive Symmetric Erythrokeratodermia

“…PSEK is characterized by early-onset, slowly progressive, symmetrical, erythematous skin plaques predominantly on the extensor aspect of the extremities, with or without palmoplantar keratoderma. Mutations in several genes, including LOR, GJB4, GJA1, KDSR, ELOVL4, and KRT83 (encoding loricrin, connexin 30.3, connexin 43, 3ketodihydrosphingosine reductase, elongation of very long chain fatty acids-like 4 and keratin 83, respectively), have been linked to PSEK (Boyden et al, 2015(Boyden et al, , 2017Cadieux-Dion et al, 2014;Ishida-Yamamoto et al, 1997;Shah et al, 2017;van Steensel et al, 2009). Here, we identified two missense mutations in TRPM4 as a previously undescribed cause of an autosomal dominanteinherited PSEK with spontaneous remission after puberty in three separate families.…”

Progressive hyperpigmented rash in a 10‐year‐old boy

“…KRT83 mutations are transmitted via autosomal recessive inheritance and have been reported in a large Pakistani family with classic clinical findings of PSEK. 4 KDSR mutations also are inherited via autosomal recessive inheritance in patients with a PSEK-like phenotype. 5 Other patients with abnormal cornification and thrombocytopenia also have been reported with KDSR mutations, 6 signifying that this gene is involved in cornification in various ways.…”

Analysis of TYR Gene Pathogenic Variants in a Chinese Mongolian Family with Progressive Symmetric Erythrokeratoderma

“…PSEK, a rare genetic keratotic skin disorder, is usually autosomal dominant but in some cases is autosomal recessive. [ 1 ] PSEK is characterised by early onset and slow progression. Symmetric erythema is mainly located on the extensor side of the extremities, with or without palmar-plantar keratosis.…”

“…Symmetric erythema is mainly located on the extensor side of the extremities, with or without palmar-plantar keratosis. [ 2 ] Researchers at home and abroad have reached different conclusions about the causative genes of PSEK, with the following genes implicated: Loricrin (LOR),[ 3 ] gap junction β4 (GJB4),[ 4 ] gap junction β2 (GJB2),[ 5 ] keratin 83 (KRT83),[ 1 ] 3-ketodihydrosphingosine reductase (KDSR),[ 6 ] and transient receptor potential melastatin 4 (TRPM4). [ 7 ] We collected blood samples from a Chinese Mongolian family with PSEK and performed whole-exome sequencing to detect gene pathogenic variants.…”