• geroderma osteodysplasticum

This report describes geroderma osteodysplastica (GO); GO exhibits autosomal recessive inheritance. The human gene implicated in this disease is GORAB, which encodes a golgin, a coiled-coil protein localized to the Golgi. There is a single orthologous gene in Drosophila, Dmel\Gorab, for which amorphic mutations created by targeted recombination and RNAi-targeting constructs have been generated.

The human GORAB gene has not been introduced into flies.

In flies the Dmel\Gorab protein has been shown to localize to the Golgi. Animals homozygous for amorphic mutations of Dmel\Gorab survive to adulthood; females are sterile; adults exhibit temperature-sensitive locomotor defects. Tissue-specific defects in centriole duplication are observed that result in defects in mechanosensory cilia. A small number of physical interactions have been described for Dmel\Gorab; see below and in the Gorab gene report.

A missense variant analogous to a human variant implicated in geroderma osteodysplastica has been assessed. This mutation prevents the Gorab protein from associating with Golgi, but fully rescues centriole and cilia defects of Gorab amorphic mutants. Thus, these two functions appear to be separable. Variant(s) implicated in human disease tested (as analogous mutation in fly gene): V266P in the fly Gorab gene [corresponds to A245P (A220P) in the human GORAB gene].

[updated Oct. 2018 by FlyBase; FBrf0222196]