- Title
- Phenotype-genotype correlations in a series of Wolfram syndrome families
- Creator
- Smith, Casey J. A.; Crock, Patricia A.; King, Bruce R.; Meldrum, Cliff J.; Scott, Rodney J.
- Relation
- Diabetes Care Vol. 27, Issue 8, p. 2003-2009
- Publisher Link
- http://dx.doi.org/10.2337/diacare.27.8.2003
- Publisher
- American Diabetes Association
- Resource Type
- journal article
- Date
- 2004
- Description
- Objective: Wolfram syndrome is an extremely rare autosomal-recessive disorder that predisposes the development of type 1 diabetes in association with progressive optic atrophy. The genetic basis of this disease has been shown to be due to mutations in the WFS1 gene. The WFS1 gene encodes a novel transmembrane protein called wolframin, which recent evidence suggests may serve as a novel endoplasmic reticulum calcium channel in pancreatic β-cells and neurons. Genotype-phenotype correlations in this syndrome are becoming apparent and may help in explaining some of the variable characteristics observed in this disease. Research Design and Methods: In this report, we have studied 13 patients with Wolfram syndrome from nine families to further define the relationship between mutation site and type with specific disease characteristics. Results: A severe phenotype was seen in patients with mutations in exon 4 and with a large deletion encompassing most of exon 8. In total, nine novel mutations were identified as well as three new silent polymorphisms. Conclusions: Similar to all other mutation reports, most causative changes identified in the WFS1 gene occurred in exon 8, and only one was identified outside this region in exon 4.
- Subject
- Wolfram syndrome; type 1 diabetes; progressive optic atrophy; WFS1 gene; wolframin; pancreatic β-cells; mutation
- Identifier
- http://hdl.handle.net/1959.13/27183
- Identifier
- uon:1443
- Identifier
- ISSN:0149-5992
- Language
- eng
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