Erythrokeratodermia Variabilis 3

Last update 08 May 2025

Basic Info

Synonyms

EKV3, ERYTHROKERATODERMIA VARIABILIS 3, ERYTHROKERATODERMIA VARIABILIS 3 (disorder)

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Introduction

MEDNIK syndrome, previously known as Erythrokeratodermia Variabilis type 3 (EKV3), has characteristics of intellectual deficit, enteropathy, sensorineural hearing loss, peripheral neuropathy, lamellar and erythrodermic ichthyosis and keratodermia. The syndrome has been described in four families descending from limited number of ancestors in Quebec. The disease is due to a mutation in the AP1S1 gene encoding the small subunit sigma1A of the AP-1 complex. Transmission is autosomal recessive.

100 Clinical Results associated with Erythrokeratodermia Variabilis 3

100 Translational Medicine associated with Erythrokeratodermia Variabilis 3

0 Patents (Medical) associated with Erythrokeratodermia Variabilis 3

Literatures (Medical) associated with Erythrokeratodermia Variabilis 3

01 Nov 2024·Journal of Molecular Medicine

Revising pathogenesis of AP1S1-related MEDNIK syndrome: a missense variant in the AP1S1 gene as a causal genetic lesion

Article

Author: Bonifacino, Juan S. ; Svaton, Michael ; Fabian, Ondrej ; Mattera, Rafael ; Park, Sang Yoon ; Skvarova Kramarzova, Karolina ; Rackova, Marketa ; Kanderova, Veronika ; Fencl, Filip ; Bonifacino, Juan S ; Fronkova, Eva ; Koblizek, Miroslav ; Spicakova, Karolina

AbstractMEDNIK syndrome is a rare autosomal recessive disease characterized by mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis, and keratoderma, and caused by variants in the adaptor-related protein complex 1 subunit sigma 1 (AP1S1) gene. This gene encodes the σ1A protein, which is a subunit of the adaptor protein complex 1 (AP-1), a key component of the intracellular protein trafficking machinery. Previous work identified three AP1S1 nonsense, frameshift and splice-site variants in MEDNIK patients predicted to encode truncated σ1A proteins, with consequent AP-1 dysfunction. However, two AP1S1 missense variants (c.269 T > C and c.346G > A) were recently reported in patients who presented with severe enteropathy but no additional symptoms of MEDNIK. This condition was described as a novel non-syndromic form of congenital diarrhea caused specifically by the AP1S1 missense variants. In this study, we report two patients with the same c.269 T > C variant, who, contrary to the previous cases, presented as complete MEDNIK syndrome. These data substantially revise the presentation of disorders associated with AP1S1 gene variants and indicate that all the identified pathogenic AP1S1 variants result in MEDNIK syndrome. We also provide a series of functional analyses that elucidate the impact of the c.269 T > C variant on σ1A function, contributing to a better understanding of the molecular pathogenesis of MEDNIK syndrome.Key messages

A missense AP1S1 c.269 T > C (σ1A L90P) variant causes full MEDNIK syndrome.

The σ1A L90P variant is largely unable to assemble into the AP-1 complex.

The σ1A L90P variant fails to bind [DE]XXXL[LI] sorting motifs.

The σ1A L90P variant results in loss-of-function of the protein.

01 Mar 2022·European Journal of Medical GeneticsQ4 · MEDICINE

Phenotypic spectrum of autosomal recessive Keratitis-Ichthyosis-Deafness Syndrome (KIDAR) due to mutations in AP1B1

Q4 · MEDICINE

Review

Author: Zoghi, Sina ; Dianatpour, Mehdi ; Kamal, Neda ; Bagher Tabei, Seyed Mohammad ; Faghihi, Fatemeh ; Dastgheib, Seyed Alireza ; Yeganeh, Babak Shirazi ; Khamirani, Hossein Jafari

Inborn errors in copper metabolism result in a diverse set of abnormalities such as Wilson disease and MEDNIK syndrome. Homozygous pathogenic variants in AP1B1 lead to KIDAR (Keratitis-Ichthyosis-Deafness Syndrome). The main phenotypic features of KIDAR are ichthyosis, keratitis, erythroderma, and progressive hearing loss accompanied by developmental delay and failure to thrive. Herein, we describe a six-and-a-half-year-old boy with KIDAR caused by a novel pathogenic variant in AP1B1 (NM_001127.4:c.1263C > A, p.Tyr421*). The proband presented with ichthyosis, erythroderma, palmoplantar keratoderma, hearing loss, and corneal scarring. He also had hypotonia, global developmental delay, and photophobia. Lastly, we review all of the previously reported cases and the clinical features associated with KIDAR.

01 May 2021·Journal of the European Academy of Dermatology and Venereology

MEDNIK‐like syndrome due to compound heterozygous mutations in AP1B1

Letter

Author: Igari, S. ; Ito, Y. ; Hosoya, M. ; Suyama, K. ; Takeuchi, S. ; Ogi, T. ; Ono, A. ; Yamamoto, T. ; Takeichi, T. ; Akiyama, M. ; Muro, Y. ; Mori, T.

A two-year-old Japanese boy, the first child born to unrelated parents with no family history of any similar disorder.A few days after birth, he was noticed to have an ichthyotic phenotype, with papules and moderate hyperkeratosis in erythrodermic skin over almost the entire body.Whole-exome sequencing showed compound heterozygous, novel nonsense mutations in AP1B1-the paternal mutation c.1852C > T (p.Gln618*), and the maternal mutation c.2596C>T (p.Gln866*)-which were confirmed by Sanger sequencing.The role of aberrant ATP7A trafficking in the pathogenesis of skin symptoms has not been clarified sufficiently.The patient with bi-allelic nonsense mutations in AP1B1 showed almost all the characteristic clin. features of the MEDNIK syndrome.The further accumulation of ichthyosis syndrome cases with AP1B1 mutations is needed to reveal genotype/phenotype correlation in AP1B1 mutations.

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Erythrokeratodermia Variabilis 3

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