NONSYNDROMIC DEAFNESS DFNA1 ASSOCIATED WITH MUTATION OF A HUMAN HOMOLOG OF THE DROSOPHILA GENE DIAPHANOUS

The gene responsible for autosomal dominant, fully penetrant, nonsyndr omic sensorineural progressive hearing loss in a large Costa Rican kin dred was previously localized to chromosome 5q31 and named DFNA1. Deaf ness in the family is associated with a protein-truncating mutation in a human homolog of the Drosophila gene diaphanous. The truncation is caused by a single nucleotide substitution in a splice donor, leading to a four-base pair insertion in messenger RNA and a frameshift, The d iaphanous protein is a profilin ligand and target of Rho that regulate s polymerization of actin, the major component of the cytoskeleton of hair cells of the inner ear.