This report describes a severe neurodevelopmental disorder postulated to be caused by de novo heterozygous variants in the human gene DROSHA. DROSHA encodes a ribonuclease that acts as a subunit of the microprocessor protein complex; this complex catalyzes the initial processing step of miRNA processing. In Drosophila there is a singe orthologous gene, also designated drosha. Multiple genetic reagents have been generated for Dmel\drosha, including classical amorphic and hypomorphic mutations and RNAi-targeting constructs.
Animals homozygous for amorphic or severe loss-of-function mutations of Dmel\drosha typically die during late larval or pupal stages; imaginal discs fail to develop; mutant larvae exhibit a severely reduced brain size. Mutations analogous to disease-implicated variants in human have been introduced into the fly gene and characterized for ability to rescue drosha loss-of-function phenotypes. See the 'Disease-Implicated Variants' table below.
A UAS construct of the wild-type human Hsap\DROSHA gene has been introduced into flies; partial heterologous rescue (functional complementation) has been demonstrated.
[updated Nov. 2022 by FlyBase; FBrf0222196]
Two characterized individuals exhibit profound intellectual disability, epilepsy, white matter atrophy, microcephaly and dysmorphic features (Barish et al. 2022; pubmed:35405010; FBrf0254695).
Described individuals carry damaging de novo heterozygous variants in DROSHA (Barish et al. 2022; pubmed:35405010; FBrf0254695).
DROSHA encodes a ribonuclease (RNase) III double-stranded RNA-specific ribonuclease and subunit of the microprocessor protein complex, which catalyzes the initial processing step of microRNA (miRNA) synthesis. [Gene Cards, DROSHA; 2022.11.04]
One to one: 1 human gene to 1 Drosophila gene.
High-scoring ortholog of human DROSHA gene (1 Drosophila to 1 human).
