J Korean Med Sci.  2010 Oct;25(10):1539-1542. 10.3346/jkms.2010.25.10.1539.

Hereditary Palmoplantar Keratoderma and Deafness Resulting from Genetic Mutation of Connexin 26

• Lee JY
• In SI
• Kim HJ
• Jeong SY
• Choung YH
• Kim YC

• KMID: 2157865
• DOI: http://doi.org/10.3346/jkms.2010.25.10.1539

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.

Keyword

Keratoderma; Palmoplantar; Hearing Loss; Connexin 26

MeSH Terms

Adult
Alleles
Amino Acid Substitution
Child, Preschool
Connexins/*genetics
DNA Mutational Analysis
Deafness/complications/*genetics
Female
Humans
Keratoderma, Palmoplantar/complications/*genetics/pathology
*Mutation
Pedigree
Skin/pathology

Figure

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  Fig. 1 Clinical features of the mother and her daughter. Keratotic plaques on the knuckle area (A, C) and diffuse hyperkeratosis of the hands (B, D) and feet (E-H); mother (A, B, E, F) and daughter (C, D, G, H).

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  Fig. 2 Histopathological features of the mother and her daughter. Biopsy specimens from the soles showed compact hyperkeratosis, acanthosis with a well-formed granular layer, consistent with the diagnosis of palmoplantar keratosis. (A) mother, (B) daughter (H&E stain, ×100).

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  Fig. 3 Pedigree chart. The maternal grandfather, mother, and aunt also had a history of hearing loss and hyperkeratosis of the palms and soles with the onset in infancy; the arrow denotes the proband.

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  Fig. 4 Mutation analysis in the mother and her daughter. Sequence analysis of the GJB2 gene shows a heterozygous c.223C>T mutation (R75W), which alters the arginine codon and tryptophan replacement (arrows). Y means C and T.

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