Journal article
Mutations in the WFS1 gene that cause low-frequency sensorineural hearing loss are small non-inactivating mutations
Human genetics, Vol.110(5), pp.389-394
05/2002
DOI: 10.1007/s00439-002-0719-1
PMID: 12073007
Abstract
Hereditary hearing impairment is an extremely heterogeneous trait, with more than 70 identified loci. Only two of these loci are associated with an auditory phenotype that predominantly affects the low frequencies (DFNA1 and DFNA6/14). In this study, we have completed mutation screening of the WFS1 gene in eight autosomal dominant families and twelve sporadic cases in which affected persons have low-frequency sensorineural hearing impairment (LFSNHI). Mutations in this gene are known to be responsible for Wolfram syndrome or DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness), which is an autosomal recessive trait. We have identified seven missense mutations and a single amino acid deletion affecting conserved amino acids in six families and one sporadic case, indicating that mutations in WFS1 are a major cause of inherited but not sporadic low-frequency hearing impairment. Among the ten WFS1 mutations reported in LFSNHI, none is expected to lead to premature protein truncation, and nine cluster in the C-terminal protein domain. In contrast, 64% of the Wolfram syndrome mutations are inactivating. Our results indicate that only non-inactivating mutations in WFS1 are responsible for non-syndromic low-frequency hearing impairment.
Details
- Title: Subtitle
- Mutations in the WFS1 gene that cause low-frequency sensorineural hearing loss are small non-inactivating mutations
- Creators
- Kim Cryns - Department of Medical Genetics, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, BelgiumMarkus Pfister - Department of Otolaryngology, University of Tübingen, Tübingen, GermanyRonald Pennings - Department of Otorhinolaryngology, University Medical Center St Radboud, Nijmegen, The NetherlandsSteven Bom - Department of Otorhinolaryngology, University Medical Center St Radboud, Nijmegen, The NetherlandsKris Flothmann - Department of Medical Genetics, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, BelgiumGoele Caethoven - Department of Medical Genetics, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, BelgiumHannie Kremer - Department of Otorhinolaryngology, University Medical Center St Radboud, Nijmegen, The NetherlandsIsabelle Schatteman - Department of Otolaryngology, Saint-Augustinus Hospital, Antwerp, BelgiumKaren Köln - Molecular Otolaryngology Research Laboratories, Department of Otolaryngology, University of Iowa, Iowa City, Iowa, USATímea Tóth - Medical and Health Science Center, Department of Otolaryngology, University of Debrecen, Debrecen, HungarySusan Kupka - Department of Otolaryngology, University of Tübingen, Tübingen, GermanyNikolaus Blin - Institute of Human Genetics and Anthropology, University of Tübingen, Tübingen, GermanyPeter Nürnberg - Gene Mapping Center (GMC), Max Delbrueck Center for Molecular Medicine (MDC), Berlin, GermanyHolger Thiele - Gene Mapping Center (GMC), Max Delbrueck Center for Molecular Medicine (MDC), Berlin, GermanyPaul Heyning - Department of Otolaryngology, University of Antwerp, Antwerp, BelgiumWilliam Reardon - National Centre for Medical Genetics, Our Lady's Hospital for Sick Children, Crumlin, Dublin, IrelandDafydd Stephens - Welsh Hearing Institute, University Hospital of Wales, Cardiff, WalesCor Cremers - Department of Otorhinolaryngology, University Medical Center St Radboud, Nijmegen, The NetherlandsRichard Smith - Molecular Otolaryngology Research Laboratories, Department of Otolaryngology, University of Iowa, Iowa City, Iowa, USAGuy Camp - Department of Medical Genetics, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium
- Resource Type
- Journal article
- Publication Details
- Human genetics, Vol.110(5), pp.389-394
- DOI
- 10.1007/s00439-002-0719-1
- PMID
- 12073007
- NLM abbreviation
- Hum Genet
- ISSN
- 0340-6717
- eISSN
- 1432-1203
- Publisher
- Springer-Verlag; Berlin/Heidelberg
- Language
- English
- Date published
- 05/2002
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Otolaryngology; Internal Medicine
- Record Identifier
- 9984006422202771
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