Mutational spectrum of the WFS1 gene in Wolfram syndrome, nonsyndromic hearing impairment, diabetes mellitus, and psychiatric disease

Kim Cryns; Theru A Sivakumaran; Jody M W Van den Ouweland; Ronald J E Pennings; Cor W R J Cremers; Kris Flothmann; Terry-Lynn Young; Richard J H Smith; Marci M Lesperance; Guy Van Camp

doi:10.1002/humu.10258

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Mutational spectrum of the WFS1 gene in Wolfram syndrome, nonsyndromic hearing impairment, diabetes mellitus, and psychiatric disease

Journal article

Peer reviewed

Mutational spectrum of the WFS1 gene in Wolfram syndrome, nonsyndromic hearing impairment, diabetes mellitus, and psychiatric disease

Kim Cryns, Theru A Sivakumaran, Jody M W Van den Ouweland, Ronald J E Pennings, Cor W R J Cremers, Kris Flothmann, Terry-Lynn Young, Richard J H Smith, Marci M Lesperance and Guy Van Camp

Human mutation, Vol.22(4), pp.275-287

10/2003

DOI: 10.1002/humu.10258

PMID: 12955714

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Abstract

WFS1 is a novel gene and encodes an 890 amino-acid glycoprotein (wolframin), predominantly localized in the endoplasmic reticulum. Mutations in WFS1 underlie autosomal recessive Wolfram syndrome and autosomal dominant low frequency sensorineural hearing impairment (LFSNHI) DFNA6/14. In addition, several WFS1 sequence variants have been shown to be significantly associated with diabetes mellitus and this gene has also been implicated in psychiatric diseases. Wolfram syndrome is highly variable in its clinical manifestations, which include diabetes insipidus, diabetes mellitus, optic atrophy, and deafness. Wolfram syndrome mutations are spread over the entire coding region, and are typically inactivating, suggesting that a loss of function causes the disease phenotype. In contrast, only non-inactivating mutations have been found in DFNA6/14 families, and these mutations are mainly located in the C-terminal protein domain. In this paper, we provide an overview of the currently known disease-causing and benign allele variants of WFS1 and propose a potential genotype-phenotype correlation for Wolfram syndrome and LFSNHI.

Alternative Splicing

Diabetes Mellitus - genetics

Membrane Proteins - genetics

Humans

Molecular Sequence Data

Hearing Loss, Sensorineural - genetics

Wolfram Syndrome - genetics

Polymorphism, Genetic

Mental Disorders - genetics

Hearing Loss, Sensorineural - diagnosis

DNA Mutational Analysis

Base Sequence

Wolfram Syndrome - diagnosis

Mutation

Databases, Nucleic Acid

Details

Title: Subtitle: Mutational spectrum of the WFS1 gene in Wolfram syndrome, nonsyndromic hearing impairment, diabetes mellitus, and psychiatric disease
Creators: Kim Cryns - Department of Medical Genetics, University of Antwerp, Antwerp, Belgium
Theru A Sivakumaran
Jody M W Van den Ouweland
Ronald J E Pennings
Cor W R J Cremers
Kris Flothmann
Terry-Lynn Young
Richard J H Smith
Marci M Lesperance
Guy Van Camp
Resource Type: Journal article
Publication Details: Human mutation, Vol.22(4), pp.275-287
DOI: 10.1002/humu.10258
PMID: 12955714
NLM abbreviation: Hum Mutat
ISSN: 1059-7794
eISSN: 1098-1004
Publisher: United States
Grant note: R01 DC01076 / NIDCD NIH HHS
Language: English
Date published: 10/2003
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: 9984006340102771

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