title: Identification of a novel COCH mutation, I109N, highlights the similar clinical features observed in DFNA9 families.
abstract: Hereditary hearing loss is a heterogeneous condition at both the genetic and clinical levels. We have recruited an Australian family with dominant sensorineural nonsyndromic late onset hearing loss. The hearing loss typically begins in the second or third decade of life as a high frequency loss which progresses to a severe to profound loss by the sixth to seventh decade. All affected family members presented with concomitant vestibular dysfunction. Vertigo is a less common feature. The causative gene in this family was identified as COCH which lies within the DFNA9 interval. We identified a new point mutation, 253 T>A, in the coding region of the COCH gene, changing the isoleucine 109 to an asparagine (I109N). This is a non-conservative change of an amino acid that is identical in the human, mouse and chicken sequences. The mutation was identified in all affected individuals (n=13) and all were heterozygotes. Hearing loss in this family is clinically similar to that observed in ten other DFNA9 families. However, there are some differences in the age of onset and the extent of vestibular involvement. The remarkable clinical uniformity observed between DFNA9 families is intriguing especially in light of the great phenotypic variability observed with some of the other hearing loss genes. Hum Mutat 117:351, 2001.
authors: The Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, Australia. kamarinm@cryptic.rch.unimelb.edu.au
authors: M
authors: M
authors: Kamarinos
authors: J
authors: J
authors: McGill
authors: M
authors: M
authors: Lynch
authors: H
authors: H
authors: Dahl
mesh_terms: D000328:Adult; D017668:Age of Onset; D000595:Amino Acid Sequence; D000818:Animals; D001315:Australia; D004252:DNA Mutational Analysis; D004244:Dizziness / Q000150:complications / Q000235:genetics; D016326:Extracellular Matrix Proteins; D005799:Genes, Dominant / Q000235:genetics; D005820:Genetic Testing; D006319:Hearing Loss, Sensorineural / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D006579:Heterozygote; D006801:Humans; D020407:Internet; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics*; D016415:Sequence Alignment
chemical_list: C110668:COCH protein, human; C491729:Coch protein, mouse; D016326:Extracellular Matrix Proteins; D011506:Proteins