• Wolfram syndrome 1

This report describes WFS1-related disorders, a range of disorders characterized by juvenile-onset diabetes, bilateral optic atrophy, hearing loss, and progressive neurologic abnormalities (or a subset of these phenotypes; see MIM:606201, MIM:222300, MIM:614296, MIM:600965). The most severe, Wolfram syndrome 1 (Wolfram syndrome 1), exhibits autosomal recessive inheritance; for other WFS1-related disorders, autosomal dominant inheritance is observed. The WFS1 gene encodes a transmembrane glycoprotein that localizes primarily to the endoplasmic reticulum. There is a single orthologous gene in Drosophila, Dmel\wfs1, for which RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated.

The human WFS1 gene has not been introduced into flies.

In Drosophila, RNAi directed against Dmel\wfs1 has been used to characterize phenotypes resulting from loss of function in neural and/or glial cells. The results suggest that reduction in wfs1 function alone does not severely disrupt cellular functions or directly cause neurodegeneration. It is postulated that wfs1 plays a protective role against various stressors associated with aging, thus, its deficiency increases the susceptibility to neurodegeneration in aged flies; expression in both neuronal and glial cells appears to be required for this protective effect. Stressors assessed include oxidative stress and two disease-related scenarios: altered neuronal excitability (see FBhh0000564) and tau-related neurodegeneration (see FBhh0000101).

[updated May 2018 by FlyBase; FBrf0222196]