title: Novel COCH mutation in a family with autosomal dominant late onset sensorineural hearing impairment and tinnitus.
abstract: This report describes a three generation family with late onset bilateral sensorineural hearing impairment (BLSNHI) and tinnitus in which a novel mutation in the COCH gene was identified after a genome-wide linkage approach. The COCH gene is one of the few genes clinically examined when investigating the etiology of autosomal dominant late onset hearing impairment. Initially mutations in the COCH gene were only reported in exons 4 and 5, coding for the LCCL protein domain. More recently, additional mutations have been identified in exon 12, the only mutations identified outside of the LCCL domain. Currently clinical genetic testing for the COCH gene primarily focuses on identifying mutations in these three exons. In this study, we identify a novel mutation in the COCH gene in exon 11, which, like the exon 12 mutations, falls within the vWFA2 protein domain. This finding reinforces the need for clinical genetic screening of the COCH gene to be expanded beyond the current limited exon screening, as there is now more evidence to support that mutations in other areas of this gene are also causative of a similar form of late onset BLSNHI.
authors: Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors: Emily
authors: E
authors: Gallant
authors: Lauren
authors: L
authors: Francey
authors: Heather
authors: H
authors: Fetting
authors: Maninder
authors: M
authors: Kaur
authors: Hakon
authors: H
authors: Hakonarson
authors: Dinah
authors: D
authors: Clark
authors: Marcella
authors: M
authors: Devoto
authors: Ian D
authors: ID
authors: Krantz
mesh_terms: D017668:Age of Onset; D004252:DNA Mutational Analysis; D003638:Deafness / Q000235:genetics; D018450:Disease Progression; D005091:Exons / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005799:Genes, Dominant; D008040:Genetic Linkage; D006319:Hearing Loss, Sensorineural / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D010375:Pedigree; D014012:Tinnitus / Q000235:genetics*
chemical_list: C110668:COCH protein, human; D016326:Extracellular Matrix Proteins