G90 A NOVEL AUTOSOMAL DOMINANT GJB2 MUTATION MANIFESTING AS HEARING IMPAIRMENT AND PALMOPLANTAR KERATODERMA

S. M. Kirke¹, C. S. Munro², A. M. Taylor¹.¹Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne, UK; ²Department of Dermatology, Southern General Hospital, Glasgow, UK

Proband: A profoundly deaf 9 year old boy of non-consanguineous parents was referred to dermatology outpatients with odd toenails. Examination revealed pitted dystrophy affecting all fingernails and most of toenails. No hyperkeratosis of nails was present. Transgradiens, diffuse, well-demarcated keratoderma involved the feet and was less marked on the hands. Brain stem evoked response audiometry performed at 2 months of age failed to elicit any response at 100 decibels and profound hearing loss was diagnosed. His 39 year old father who was profoundly deaf from birth had a mild palmar/plantar keratoderma while his 36 year old mother, also profoundly deaf, had normal skin. His 12 year old sister had normal hearing and normal skin. This patient’s keratoderma improved with the use of standard topical agents and at 6 years from presentation his skin shows a mild keratoderma on his feet and little detectable abnormality on his hands.

Investigations: Mutation analysis showed the proband to be double heterozygous for two sequence variants of genes coding for connexion 26 (GJB2), 35delG, and a new mutation, 125del AGG. His mother was homozygous for 35delG and his sister heterozygous for it. His father was heterozygous for the 125delAGG mutation.

Discussion: 125delAGG is the fourth reported autosomal dominant mutation of GJB2 that results in hearing impairment and palmoplantar keratoderma. The mutation is predicted to eliminate the amino acid residue E42 in connexion 26. Mutations in GJB2 are the leading cause of autosomal recessive non-syndromic hearing imparment (for example 35delG) whereas dominant mutations in the genes encoding the connexins important for hearing manifest with a spectrum of clinical phenotypes affecting hearing …