A novel WFS1 mutation in a family with dominant low frequency sensorineural hearing loss with normal VEMP and EcochG findings
Open Access
- 2 June 2008
- journal article
- Published by Springer Science and Business Media LLC in BMC Medical Genetics
- Vol. 9 (1), 48
- https://doi.org/10.1186/1471-2350-9-48
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.Keywords
This publication has 36 references indexed in Scilit:
- Sodium-potassium ATPase 1 subunit is a molecular partner of Wolframin, an endoplasmic reticulum protein involved in ER stressHuman Molecular Genetics, 2007
- Protein structure prediction servers at University College LondonNucleic Acids Research, 2005
- Protein secondary structure prediction based on position-specific scoring matrices 1 1Edited by G. Von HeijneJournal of Molecular Biology, 1999
- Saccular Dysfunction in Ménière's Patients: A Vestibular‐Evoked Myogenic Potential StudyAnnals of the New York Academy of Sciences, 1999
- GenTHREADER: an efficient and reliable protein fold recognition method for genomic sequencesJournal of Molecular Biology, 1999
- p190-B, a New Member of the Rho GAP Family, and Rho Are Induced to Cluster after Integrin Cross-linkingJournal of Biological Chemistry, 1995
- A gene for autosomal dominant nonsyndromic hereditary hearing impairment maps to 4p16.3Human Molecular Genetics, 1995
- Molecular Genetic Analysis of Distal Mouse Chromosome 6 Defines Gene Order and Positions of the deafwaddler and opisthotonos MutationsGenomics, 1995
- A Model Recognition Approach to the Prediction of All-Helical Membrane Protein Structure and TopologyBiochemistry, 1994
- High-Frequency Audiometry: Age and sex variationsScandinavian Audiology, 1979