Original Paper

Genotype-Phenotype Correlation for DFNA22: Characterization of Non-Syndromic, Autosomal Dominant, Progressive Sensorineural Hearing Loss due to MYO6 Mutations
Vedat Topsakal^{a, c}, Nele Hilgert^b, Joost van Dinther^d, Lisbeth Tranebjærg^{e, f}, Nanna D. Rendtorff^e, Andrzej Zarowski^d, Erwin Offeciers^d, Guy Van Camp^b, Paul van de Heyning<sup>c

a</sup>Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center Utrecht, Utrecht, The Netherlands;
^bDepartment of Medical Genetics, University of Antwerp, and
^cDepartment of Otorhinolaryngology, Antwerp University Hospital, University of Antwerp, Antwerp, and
^dUniversity ENT Department, Sint-Augustinus Hospital, Wilrijk, Antwerp, Belgium;
^eWilhelm Johannsen Centre for Functional Genome Research, Department of Cellular and Molecular Medicine, Panum Institute, University of Copenhagen, and
^fDepartment of Audiology, Bispebjerg Hospital, Copenhagen, Denmark

Address of Corresponding Author

Audiol Neurotol 2010;15:211-220 (DOI: 10.1159/000255339)

  Key Words

• Age-related typical audiograms
• DFNA22
• Myosin VI
• Autosomal dominant sensorineural hearing loss
• Hereditary hearing impairment

  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.

Copyright © 2009 S. Karger AG, Basel

  Author Contacts

Vedat Topsakal, MD, PhD
Department of Otorhinolaryngology Head and Neck Surgery, UMC Utrecht
Heidelberglaan 100, PO Box 85500, Room G05.129
NL-3508 CX Utrecht (The Netherlands)
Tel. +31 88 75 577 17, Fax +31 30 25 419 22, E-Mail v.topsakal@umcutrecht.nl

  Article Information

Received: June 24, 2009
Accepted after revision: August 19, 2009
Published online: November 5, 2009
Number of Print Pages : 10
Number of Figures : 5, Number of Tables : 0, Number of References : 26