Journal article
Autoimmune Disease in a DFNA6/14/38 Family carrying a Novel Missense Mutation in WFS1
American journal of medical genetics. Part A, Vol.146A(17), pp.2258-2265
09/01/2008
DOI: 10.1002/ajmg.a.32449
PMCID: PMC2586182
PMID: 18688868
Abstract
Most familial cases of autosomal dominant low frequency sensorineural hearing loss (LFSNHL) are attributable to mutations in the Wolframin syndrome 1 (
WFS1
) gene at the DFNA6/14/38 locus.
WFS1
mutations at this locus were first described in 2001 in six families segregating LFSNHL that was non-progressive below 2000 Hz; the causative mutations all clustered in the C-terminal domain of the wolframin protein. Mutations in
WFS1
also cause Wolfram syndrome (WS), an autosomal recessive neurodegenerative disorder defined by diabetes mellitus, optic atrophy and often deafness, while numerous single nucleotide polymorphisms (SNPs) in
WFS1
have been associated with increased risk for diabetes mellitus, psychiatric illnesses and Parkinson’s disease.
This study was conducted in an American family segregating autosomal dominant LFSNHL. Two hearing impaired family members also had autoimmune diseases - Graves disease (GD) and Crohn’s disease (CD). Based on the low frequency audioprofile, mutation screening of
WFS1
was completed and a novel missense mutation (c.2576G→A) that results in an arginine-to-glutamine substitution (p.R859Q) was identified in the C-terminal domain of the wolframin protein where most LFSNHL-causing mutations cluster. The family member with GD also carried polymorphisms in
WFS1
that have been associated with other autoimmune diseases.
Details
- Title: Subtitle
- Autoimmune Disease in a DFNA6/14/38 Family carrying a Novel Missense Mutation in WFS1
- Creators
- Michael S Hildebrand - Department of Otolaryngology - Head and Neck Surgery, University of Iowa, Iowa City, IA, USAJessica L Sorensen - Department of Otolaryngology - Head and Neck Surgery, University of Iowa, Iowa City, IA, USAMaren Jensen - Department of Genetics, Boys Town National Research Hospital, Omaha, NE, USAWilliam J Kimberling - Department of Genetics, Boys Town National Research Hospital, Omaha, NE, USARichard J.H Smith - Department of Otolaryngology - Head and Neck Surgery, University of Iowa, Iowa City, IA, USA
- Resource Type
- Journal article
- Publication Details
- American journal of medical genetics. Part A, Vol.146A(17), pp.2258-2265
- DOI
- 10.1002/ajmg.a.32449
- PMID
- 18688868
- PMCID
- PMC2586182
- NLM abbreviation
- Am J Med Genet A
- ISSN
- 1552-4825
- eISSN
- 1552-4833
- Language
- English
- Date published
- 09/01/2008
- 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
- 9984006342702771
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