Wolfram syndrome and WFS1 gene
Article first published online: 25 AUG 2010
© 2010 John Wiley & Sons A/S
Volume 79, Issue 2, pages 103–117, February 2011
How to Cite
Rigoli, L., Lombardo, F. and Di Bella, C. (2011), Wolfram syndrome and WFS1 gene. Clinical Genetics, 79: 103–117. doi: 10.1111/j.1399-0004.2010.01522.x
- Issue published online: 6 JAN 2011
- Article first published online: 25 AUG 2010
- Accepted manuscript online: 12 AUG 2010 01:20PM EST
- Received 27 April 2010, revised and accepted for publication 27 July 2010
- autosomal recessive inheritance;
- WFS1 gene;
- Wolfram syndrome
Rigoli L, Lombardo F, Di Bella C. Wolfram syndrome and WFS1 gene.
Wolfram syndrome (WS) (MIM 222300) is a rare multisystem neurodegenerative disorder of autosomal recessive inheritance, also known as DIDMOAD (diabetes insipidus, insulin-deficient diabetes mellitus, optic atrophy and deafness). A Wolfram gene (WFS1) has been mapped to chromosome 4p16.1 which encodes an endoplasmic reticulum (ER) membrane-embedded protein. ER localization suggests that WFS1 protein has physiological functions in membrane trafficking, secretion, processing and/or regulation of ER calcium omeostasis. Disturbances or overloading of these functions induce ER stress responses, including apoptosis. Most WS patients carry mutations in this gene, but some studies provided evidence for genetic heterogeneity, and the genotype–phenotype relationships are not clear. Here we review the data regarding the mechanisms and the mutations of WFS1 gene that relate to WS.