A novel WFS1 mutation in a family with dominant low frequency sensorineural hearing loss with normal VEMP and EcochG findings

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A novel WFS1 mutation in a family with dominant low frequency sensorineural hearing loss with normal VEMP and EcochG findings

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dc.contributor.author Bramhall, Naomi F. en_US
dc.contributor.author Kallman, Jeremy C. en_US
dc.contributor.author Verrall, Aimee M. en_US
dc.contributor.author Street, Valerie A. en_US
dc.date.accessioned 2010-05-06T20:06:57Z
dc.date.available 2010-05-06T20:06:57Z
dc.date.issued 2008 en_US
dc.identifier.citation Bramhall N, Kallman J, Verrall A, Street V. A novel WFS1 mutation in a family with dominant low frequency sensorineural hearing loss with normal VEMP and EcochG findings. BMC Medical Genetics. 2008;9(1):48. en_US
dc.identifier.other 10.1186/1471-2350-9-48 en_US
dc.identifier.uri http://www.biomedcentral.com/1471-2350/9/48 en_US
dc.identifier.uri http://hdl.handle.net/1773/15852
dc.description.abstract Background: Low frequency sensorineural hearing loss (LFSNHL) is an uncommon clinical finding. Mutations within three different identified genes (DIAPH1, MYO7A, and WFS1) are known to cause LFSNHL. The majority of hereditary LFSNHL is associated with heterozygous mutations in the WFS1 gene (wolframin protein). The goal of this study was to use genetic analysis to determine if a small American family's hereditary LFSNHL is linked to a mutation in the WFS1 gene and to use VEMP and EcochG testing to further characterize the family's audiovestibular phenotype. Methods: The clinical phenotype of the American family was characterized by audiologic testing, vestibular evoked myogenic potentials (VEMP), and electrocochleography (EcochG) evaluation. Genetic characterization was performed by microsatellite analysis and direct sequencing of WFS1 for mutation detection. Results: Sequence analysis of the WFS1 gene revealed a novel heterozygous mutation at c.2054G>C predicting a p.R685P amino acid substitution in wolframin. The c.2054G>C mutation segregates faithfully with hearing loss in the family and is absent in 230 control chromosomes. The p.R685 residue is located within the hydrophilic C-terminus of wolframin and is conserved across species. The VEMP and EcochG findings were normal in individuals segregating the WFS1 c.2054G>C mutation. Conclusion: We discovered a novel heterozygous missense mutation in exon 8 of WFS1 predicting a p.R685P amino acid substitution that is likely to underlie the LFSNHL phenotype in the American family. For the first time, we describe VEMP and EcochG findings for individuals segregating a heterozygous WFS1 mutation. en_US
dc.description.sponsorship NIH grants DC04945 (V.A.S), DC006901 (V.A.S.) and P30 DC04661 (V.M. Bloedel Core). en_US
dc.language.iso en_US en_US
dc.title A novel WFS1 mutation in a family with dominant low frequency sensorineural hearing loss with normal VEMP and EcochG findings en_US
dc.type Article en_US


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