This report describes neurodevelopmental disorder with cerebellar atrophy and motor dysfunction (NEDCAM); NEDCAM exhibits autosomal recessive inheritance. The human gene implicated in this disease is GEMIN5, which encodes the the snRNA-binding component of the SMN complex; the SMN complex is required for the assembly of small nuclear ribonucleoproteins (snRNPs) into the spliceosome and may mediate the assembly of other classes of ribonucleoproteins. There is a single orthologous gene in Drosophila, rig, for which multiple genetic reagents, including RNAi targeting constructs and alleles caused by insertional mutagenesis, have been generated.
The human GEMIN5 gene has not been introduced into flies.
Animals homozygous for Dmel\rig loss-of-function mutations typically die during the larval or prepupal stage. Using an inducible RNAi system mediated via feeding, ubiquitous knockdown of rig from the earliest larval stage results in lethality during the pupal stage; neuroanatomy defects are observed in the larval neuromuscular junction (NMJ). Knockdown of rig during the adult stage results in locomotor dysfunctions and reduced lifespan. Physical interactions with Dmel\rig have been described; see below and in the rig gene report.
See also the human disease model report 'spinal muscular atrophy, SMN-related' (FBhh0000352).
[updated Jun. 2021 by FlyBase; FBrf0222196]
[NEURODEVELOPMENTAL DISORDER WITH CEREBELLAR ATROPHY AND MOTOR DYSFUNCTION; NEDCAM](https://omim.org/entry/619333)
[GEM NUCLEAR ORGANELLE-ASSOCIATED PROTEIN 5; GEMIN5](https://omim.org/entry/607005)
Neurodevelopmental disorder with cerebellar atrophy and motor dysfunction (NEDCAM) is an autosomal recessive disorder characterized by global developmental delay with prominent motor abnormalities, mainly axial hypotonia, gait ataxia, and appendicular spasticity. Affected individuals have cognitive impairment and speech delay; brain imaging shows cerebellar atrophy. The severity is variable (summary by Kour et al., 2021; pubmed:33963192). [from MIM:619333; 2021.06.08]
Neurodevelopmental disorder with cerebellar atrophy and motor dysfunction (NEDCAM) is caused by homozygous or compound heterozygous mutation in the GEMIN5 gene. [from MIM:619333; 2021.06.08]
GEMIN5 encodes a WD repeat protein that is a component of the survival of motor neurons (SMN) complex. The SMN complex plays a critical role in mRNA splicing through the assembly of spliceosomal small nuclear ribonucleoproteins (snRNPs), and may also mediate the assembly and transport of other classes of ribonucleoproteins. The GEMIN5 protein is the snRNA-binding component of the SMN complex. [Gene Cards, GEMIN5; 2021.06.08]
One to one: 1 human gene to 1 Drosophila gene.
Moderate-scoring ortholog of human GEMIN5 (1 Drosophila to 1 human). Dmel\rig shares 20% identity and 33% similarity with the human gene.
