Wolfram Syndrome- Rare Genetic Syndrome

Wolfram syndrome

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Wolfram syndrome (WFS) is an example of a rare genetic syndrome resulting from balletic mutation of WFS1 gene. The prevalence of WFS in the European population is very low (about 1/500,000 to 1/770,000). In all of the WFS patients diabetes mellitus together with optic nerve atrophy are observed. No causal treatment is currently available in this syndrome.

WFS is caused by recessive mutations in the WFS1 gene localized on chromosome 4p16.1 [3]. Wolframin – as a product of WFS1 gene – is an integral component of the endoplasmic reticulum and is expressed in many tissues and organs (e.g., brain, heart, pancreas, liver, muscles). This wide tissue distribution of wolframin contributes to the pleiotropic effects of mutations of the WFS1 gene. Wolframin is in fact a kind of “gatekeeper” that protects cells from ER (endoplasmic reticulum) stress which occurs due to accumulation of endogenous protein synthesis products. Thus, the loss of its function in particular cells implies an increased ER stress resulting in apoptosis of the affected cells and many neurodegenerative and endocrine symptoms. Currently, above 200 mutations resulting in WFS have been described.

Some of them are the mutations of premature termination codons (PTCs). It seems that some prospects for the causal treatment of patients with WFS can give a recently discovered phenomenon – a readthrough of PTCs. The use of a chemical compound that bypasses premature stop codons (stop codons are reading as glycine) results in a continuation of translation. Chemical compounds with the above described properties are e.g. aminoglycosides, including gentamicin. However, they have numerous side effects [7,8]. Ataluren (formerly PTC124), another readthrough-promoting compound, is less toxic and was approved to treat patients with Duchenne muscular dystrophy who have a nonsense mutation in the dystrophin gene.

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Christiane zweier

Senior Journal coordinator

Journal of genetic Syndromes & Gene Therapy