• syndromic intellectual disability

This report describes neurodevelopmental disorder, PRPF19-related, an autosomal dominant intellectual developmental disorder that has been associated with de novo missense mutations. The human gene implicated is PRPF19, which encodes pre-mRNA processing factor 19, a component of the Prp19 complex and U2-type catalytic step 2 spliceosome, which is involved in pre-mRNA splicing. There is one high-scoring fly ortholog, Dmel\Prp19, for which multiple genetic reagents, including classical alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis, have been generated.

Multiple UAS constructs of the human Hsap\PRPF19 gene, including wild-type Hsap\PRPF19 and genes carrying mutational lesions, have been introduced into flies. See the 'Disease-Implicated Variants' table below. Partial heterologous rescue (functional complementation) has been demonstrated for the lethality and mushroom body phenotypes observed for pan-neuronal knockdown of Dmel\Prp19.

Pan-neuronal RNAi-mediated knockdown of Dmel\Prp19 is lethal prior to eclosion, and results in a generalized reduction in brain cell proliferation, with structural morphology defects of the larval mushroom body. Affected larvae exhibit hypoactivity in crawling behavior. Overexpression of wild-type or missense variant Hsap\PRPF19, but not a variant resulting in a truncated protein, fully rescue the survival rate and partially rescue mushroom body defects. Female adults in which pan-neuronal knockdown of Dmel\Prp19 was rescued with Hsap\PRPF19 missense variants exhibit changes in social space behavior, clustering closer to neighboring flies than do wild-type flies, which disperse throughout available space (FBrf0258439).

[updated Mar. 2024 by FlyBase; FBrf0222196]