Document Detail

Mutational spectrum of the WFS1 gene in Wolfram syndrome, nonsyndromic hearing impairment, diabetes mellitus, and psychiatric disease.
MedLine Citation:
PMID:  12955714     Owner:  NLM     Status:  MEDLINE    
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.
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
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Review    
Journal Detail:
Title:  Human mutation     Volume:  22     ISSN:  1098-1004     ISO Abbreviation:  Hum. Mutat.     Publication Date:  2003 Oct 
Date Detail:
Created Date:  2003-09-04     Completed Date:  2004-04-12     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9215429     Medline TA:  Hum Mutat     Country:  United States    
Other Details:
Languages:  eng     Pagination:  275-87     Citation Subset:  IM    
Copyright Information:
Copyright 2003 Wiley-Liss, Inc.
Department of Medical Genetics, University of Antwerp, Antwerp, Belgium.
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MeSH Terms
Alternative Splicing
Base Sequence
DNA Mutational Analysis
Databases, Nucleic Acid
Diabetes Mellitus / genetics*
Hearing Loss, Sensorineural / diagnosis,  genetics*
Membrane Proteins / genetics*
Mental Disorders / genetics*
Molecular Sequence Data
Polymorphism, Genetic
Wolfram Syndrome / diagnosis,  genetics*
Grant Support
Reg. No./Substance:
0/Membrane Proteins; 0/wolframin protein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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