• syndrome

The human gene DONSON is implicated in two forms of microcephalic dwarfism (see MIM:611428; FBhh0000901); both forms exhibit autosomal recessive inheritance. DONSON encodes a replisome component that maintains genome stability by protecting stalled or damaged replication forks. Mutations in genes encoding proteins involved in DNA replication or genome stability are a frequent cause of microcephalic dwarfism. In Drosophila, there is a single ortholog of DONSON, hd, for which loss-of-function mutations, an RNAi targeting construct, and an allele caused by insertional mutagenesis have been generated.

The human DONSON gene has not been introduced into flies.

Animals with an amorphic genotype for Dmel\hd typically die during the larval stage; they have small brains that display severely reduced levels of DNA synthesis, no identifiable imaginal discs, and small, under-replicated polytene chromosomes in the salivary glands. An extensively characterized missense mutation is viable, but adult females are sterile, exhibiting impaired amplification of eggshell protein genes in the ovary. Such tissue-specific sensitivity to the effects of a mild hypomorphic mutation is reminiscent of the different pleiotropic clinical presentations observed for human microcephalic dwarfism syndromes; this aspect of the fly model may facilitate characterization of molecular mechanisms underlying the varying impact and effects of DONSON disease variants. A small number of physical interactions have been described for Dmel\hd; see below and in the hd gene report.

[updated Sep. 2018 by FlyBase; FBrf0222196]