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

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, sev...

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Bibliographic Details
Published in:Human mutation 2003-10, Vol.22 (4), p.275-287
Main Authors: Cryns, Kim, Sivakumaran, Theru A., Van den Ouweland, Jody M.W., Pennings, Ronald J.E., Cremers, Cor W.R.J., Flothmann, Kris, Young, Terry-Lynn, Smith, Richard J.H., Lesperance, Marci M., Camp, Guy Van
Format: Article
Language:English
Subjects:
Alternative Splicing
Base Sequence
Databases, Nucleic Acid
DFNA14
DFNA6
diabetes mellitus
Diabetes Mellitus - genetics
DNA Mutational Analysis
genotype-phenotype correlation
Hearing Loss, Sensorineural - diagnosis
Hearing Loss, Sensorineural - genetics
Humans
Membrane Proteins - genetics
Mental Disorders - genetics
Molecular Sequence Data
Mutation
Polymorphism, Genetic
psychiatric diseases
WFS1
WFS2
Wolfram syndrome
Wolfram Syndrome - diagnosis
Wolfram Syndrome - genetics
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Summary: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. Hum Mutat 22:275–287, 2003. © 2003 Wiley‐Liss, Inc.
ISSN:1059-7794
1098-1004
DOI:10.1002/humu.10258