title: Genotype-phenotype correlation for DFNA22: characterization of non-syndromic, autosomal dominant, progressive sensorineural hearing loss due to MYO6 mutations.
abstract: Clinical and audiological examination was done in 2 Belgian families with autosomal dominant sensorineural hearing loss (SNHL) linked to DFNA22. Nineteen subjects in family 1 had mild to moderate SNHL starting in the third decade. The hearing loss was characterized by a flat audiogram affecting all tested frequencies with statistically significant progression. In family 2 eleven subjects were affected with mild to moderate SNHL starting in the second decade. Most of them showed a flat audiogram, but some had mid-frequency hearing loss. Significant progression of thresholds was present at 4 and 8 kHz. For all hitherto known DFNA22 families the audiological and clinical characteristics were correlated with the molecular data. This study describes the phenotype of 2 Belgian families with SNHL linked to DFNA22, both with a pathogenic change in the deafness gene MYO6. The phenotypes of all hitherto reported DFNA22 families with mutations in the MYO6 gene have been studied and compared. It seems that genetic defects that spare the motor domain of the myosin VI protein have a milder phenotype.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center Utrecht, Utrecht, The Netherlands. v.topsakal@umcutrecht.nl
authors.forename: Vedat
authors.initials: V
authors.lastname: Topsakal
authors.forename: Nele
authors.initials: N
authors.lastname: Hilgert
authors.forename: Joost
authors.initials: J
authors.lastname: van Dinther
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Tranebjaerg
authors.forename: Nanna D
authors.initials: ND
authors.lastname: Rendtorff
authors.forename: Andrzej
authors.initials: A
authors.lastname: Zarowski
authors.forename: Erwin
authors.initials: E
authors.lastname: Offeciers
authors.forename: Guy
authors.initials: G
authors.lastname: Van Camp
authors.forename: Paul
authors.initials: P
authors.lastname: van de Heyning
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001309:Auditory Threshold; D001530:Belgium; D002648:Child; D002869:Chromosome Aberrations; D004252:DNA Mutational Analysis; D003638:Deafness / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant / Q000235:genetics*; D006580:Genetic Carrier Screening; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D025121:Myosin Type IV / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D055815:Young Adult
chemical_list: D025121:Myosin Type IV