• nervous system disease

In human, the DYNC1H1 gene is implicated in several neurodevelopmental and neuromuscular disorders: a form of complex cortical dysplasia (MIM:614563; FBhh0001597), a type of spinal muscular atrophy (MIM:158600; FBhh0001599); and Charcot-Marie-Tooth disease, axonal, type (MIM:614228; FBhh0001598). All exhibit autosomal dominant inheritance. DYNC1H1 encodes a member of the cytoplasmic dynein heavy chain family. There is a single orthologous gene in Drosophila, Dhc64C, for which multiple genetic reagents have been generated, including loss-of-function mutations, RNAi-targeting constructs, alleles caused by insertional mutagenesis, and CRISPR-mediated knockout and overexpression genotypes.

The human DYNC1H1 gene has not been introduced into flies.

Animals carrying severe loss-of-function mutations of Dhc64C typically die during embryonic or larval stages. Less severe mutations allow survival to adulthood, but females often exhibit reduced fertility due to deleterious maternal effects. Using analogous mutations introduced into the Drosophila gene, a number of disease-implicated variants of DYNC1H1 have been assessed; see the 'Disease-Implicated Variants' table, below. Lethality and/or abnormalities are observed in homozygous animals, but not heterozygous animals; the equivalent mutations in human or mouse cause neurological disease when heterozygous. Phenotypes observed in axons support a hypothesis that these mutations affect motility of cargo-motor complexes in neurons.

[updated Aug. 2024 by FlyBase; FBrf0222196]