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Hereditary palmoplantar keratoderma and deafness resulting from genetic mutation of Connexin 26.

ABSTRACT: Gap junctions, which mediate rapid intercellular communication, consist of connexins, small transmembrane proteins that belong to a large family of proteins found throughout the species. Mutations in the GJB2 gene, encoding Connexin 26, can cause nonsyndromic autosomal recessive or dominant hearing loss with or without skin manifestations. A 3-yr-old Korean female and her mother presented to our clinic with diffuse hyperkeratosis of the palms and soles (May 3, 2007). Skin biopsies from the soles of both patients demonstrated histopathological evidence of palmoplantar keratoderma. The patient and a number of her maternal family members also had congenital hearing loss. The combination of congenital hearing loss and palmoplantar keratoderma, inherited as an autosomal dominant trait, led us to test for a mutation in the GJB2 gene in both patients. The results showed the R75W mutation of the GJB2 gene in both. In conclusion, the simultaneous occurrence of a GJB2 mutation in a mother and daughter suggests that R75W mutation cause autosomal dominant hearing loss presenting with palmoplantar keratoderma. To the best of our knowledge, this is the first report of a GJB2 mutation associated with syndromic autosomal dominant hearing loss and palmoplantar keratoderma in a Korean family.

SUBMITTER: Lee JY

PROVIDER: S-EPMC2946671 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Hereditary palmoplantar keratoderma and deafness resulting from genetic mutation of Connexin 26.

Lee Jae Yeol JY In Sung-Il SI Kim Hyon J HJ Jeong Seon-Yong SY Choung Yun Hoon YH Kim You Chan YC

Journal of Korean medical science 20100917 10

Gap junctions, which mediate rapid intercellular communication, consist of connexins, small transmembrane proteins that belong to a large family of proteins found throughout the species. Mutations in the GJB2 gene, encoding Connexin 26, can cause nonsyndromic autosomal recessive or dominant hearing loss with or without skin manifestations. A 3-yr-old Korean female and her mother presented to our clinic with diffuse hyperkeratosis of the palms and soles (May 3, 2007). Skin biopsies from the soles ...[more]

PMID: 20890442

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Project description:ImportancePalmoplantar keratoderma poses diagnostic challenges due to its clinical and genetic heterogeneity, and knowledge on the value of systematic genetic testing on clinically well-described patient cohorts is sparse.ObjectiveTo improve knowledge of the clinical and genetic spectrum of patients with palmoplantar keratoderma.Design, setting, and participantsThis cohort study prospectively recruited patients and affected family members with palmoplantar keratoderma between September 1, 2016, and December 31, 2022. Patients were recruited from private practitioners in dermatology and dermatology departments in Denmark. Study participants were patients 18 years or older either newly diagnosed with palmoplantar keratoderma or being followed up for the disease at referral centers.Main outcomes and measuresPhenotypes and clinical subtypes were classified. Genetic testing was performed by whole-exome or genome sequencing using an in silico panel containing genes related to palmoplantar keratoderma, or by Sanger sequencing for specific variants. Descriptive analysis, such as proportions and frequency, were used to describe clinical characteristics, distribution of disease-causing variants, and genotype-phenotype associations.ResultsThis study included 142 study participants from 76 families (90 [63%] female; median [range] age, 52 [18-92] years). Clinical subtypes included 42 punctate (55%), 26 diffuse (34%), 5 focal (7%), and 3 striate (4%). A genetic diagnosis was found in 63 of 76 families (83%), including 27 disease-causing variants within 13 different genes: AAGAB (n = 39), DSG1 (n = 8), KRT1 (n = 3), DSP (n = 2), KRT9 (n = 2), AQP5 (n = 2), KRT16 (n = 1), SERPINA12 (n = 1), ABCA12 (n = 1), COL7A1 (n = 1), CARD14 (n = 1), DST (n = 1), and LORICRIN (n = 1). All participants with AAGAB variants presented with punctate palmoplantar keratoderma, showing a clear genotype-phenotype correlation. The other subtypes (diffuse, focal, and striate) proved more challenging to clinically subclassify, and disease-causing variants were identified in 12 genes, contributing to more complex genotype-phenotype patterns. Patients with palmoplantar keratoderma due to DSP variants were found, which is important to identify because of an associated risk of cardiomyopathy.Conclusion and relevanceThis study provides novel insights into the clinical and genetic spectrum of patients with palmoplantar keratoderma. It demonstrates the value of genetic testing for accurate diagnoses and to distinguish between different subtypes. The established and well-described cohort lays the foundation for future research in palmoplantar keratoderma.

Dataset Information

Hereditary palmoplantar keratoderma and deafness resulting from genetic mutation of Connexin 26.

Publications

Hereditary palmoplantar keratoderma and deafness resulting from genetic mutation of Connexin 26.

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