This report describes neurodevelopmental disorder with spasticity and poor growth (NEDSG), which shares many features with spinocerebellar ataxia; NEDSG exhibits autosomal recessive inheritance. The human gene implicated in this disease is UFC1 (ubiquitin-fold modifier conjugating enzyme 1), which functions in post-translational-modification processes. There is a single orthologous gene in Drosophila, Dmel\Ufc1, for which RNAi-targeting constructs and an allele caused by insertional mutagenesis have been generated.
Several genes (UFM1, UBA5, and UFC1) that have roles in a common ubiquitination-like post-translational-modification process have been tentatively implicated in development of autosomal recessive spinocerebellar ataxia (see FBhh0000613 and FBhh0000615). In flies, RNAi-effected knockdown of any of the three orthologous genes results in similar phenotypes.
The human UFC1 gene has not been introduced into flies.
Ubiquitous knockdown of Dmel\Ufc1 effected by RNAi results in adults with visible phenotypes, locomotor defects, and shortened lifespan. Neuron-specific knockdown results in neuroanatomical defects in larval neuromuscular junctions.
[updated Sep. 2018 by FlyBase; FBrf0222196]
[NEURODEVELOPMENTAL DISORDER WITH SPASTICITY AND POOR GROWTH; NEDSG](https://omim.org/entry/618076)
[UBIQUITIN-FOLD MODIFIER-CONJUGATING ENZYME 1; UFC1](https://omim.org/entry/610554)
The originally described patients presented with axial hypotonia, delayed psychomotor development, poor feeding, and failure to thrive. They developed peripheral spasticity with hyperreflexia and were unable to walk, sit, speak, or grasp. They had poor overall growth, and most had microcephaly. [from MIM:618076; 2018.09.14]
Neurodevelopmental disorder with spasticity and poor growth (NEDSG) is caused by homozygous mutation in the UFC1 gene. [from MIM:618076; 2018.09.14]
UFM1, UBA5, and UFC1 have roles in a common ubiquitination-like post-translational-modification process: UFM1 is a ubiquitin-like protein that is conjugated to target proteins by E1-like activating enzyme UBA5 and E2-like conjugating enzyme UFC1 in a manner analogous to ubiquitylation. This post-translational modification of proteins may play a crucial role in a number of cellular processes, such as nuclear receptors-mediated transcription and the cellular response to endoplasmic reticulum stress. [Gene Cards, UFM1; 2017.09.13]
One to one: 1 human to 1 Drosophila.
High-scoring ortholog of human gene UFC1 (1 Drosophila to 1 human); Dmel\Ufc1 shares 79% identity and 94% similarity with the human gene.
