RGD Reference Report - A missense mutation in connexin26, D66H, causes mutilating keratoderma with sensorineural deafness (Vohwinkel's syndrome) in three unrelated families.

General

A missense mutation in connexin26, D66H, causes mutilating keratoderma with sensorineural deafness (Vohwinkel's syndrome) in three unrelated families.
Authors:	Maestrini, E Korge, BP Ocana-Sierra, J Calzolari, E Cambiaghi, S Scudder, PM Hovnanian, A Monaco, AP Munro, CS
Citation:	Maestrini E, etal., Hum Mol Genet. 1999 Jul;8(7):1237-43.
RGD ID:	7364824
Pubmed:	PMID:10369869 (View Abstract at PubMed)
The multiplicity of functions served by intercellular gap junctions is reflected by the variety of phenotypes caused by mutations in the connexins of which they are composed. Mutations in the connexin26 (Cx26) gene ( GJB2 ) at 13q11-q13 are a major cause of autosomal recessive hearing loss (DFNB1), but have also been reported in autosomal dominant deafness (DFNA3). We now report a Cx26 mutation in three families with mutilating keratoderma and deafness [Vohwinkel's syndrome (VS; MIM 124500), as originally described]. VS is characterized by papular and honeycomb keratoderma associated with constrictions of digits leading to autoamputation, distinctive starfish-like acral keratoses and moderate degrees of deafness. In a large British pedigree, we have mapped the defect to the Cx26 locus. All 10 affected members were heterozygous for a non-conservative mutation, D66H, in Cx26. The same mutation was found subsequently in affected individuals from two unrelated Spanish and Italian pedigrees segregating VS, suggesting that D66H in Cx26 is a common mutation in classical VS. This mutation occurs at a highly conserved residue in the first extracellular domain of the Cx26 molecule, and may exert its effects by interfering with assembly into connexons, docking with adjacent cells or gating properties of the gap junction. Our results provide evidence that a specific mutation in Cx26 can impair epidermal differentiation, as well as inner ear function.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
Vohwinkel syndrome		IAGP		7364824	DNA:mutation:cds:p.D66H(human)	RGD
Vohwinkel syndrome		ISO	GJB2 (Homo sapiens)	7364824; 7364824	DNA:mutation:cds:p.D66H(human)	RGD

Objects Annotated

Genes (Rattus norvegicus)

Gjb2 (gap junction protein, beta 2)

Genes (Mus musculus)

Gjb2 (gap junction protein, beta 2)

Genes (Homo sapiens)

GJB2 (gap junction protein beta 2)

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A missense mutation in connexin26, D66H, causes mutilating keratoderma with sensorineural deafness (Vohwinkel's syndrome) in three unrelated families.