This report describes Vici syndrome (VICIS); VICIS exhibits autosomal recessive inheritance. The human gene implicated in this disease is EPG5, which plays a role in autophagy. Pan-neuronal RNAi knockdown is fully viable, but results in shortened adult lifespan, and a progressive decline in climbing activity.There is a single fly ortholog, Dmel\Epg5, for which RNAi-targeting constructs, alleles caused by insertional mutagenesis, and CRISPR-mediated knockout alleles have been generated.
The human EPG5 gene has not been introduced into flies.
RNAi knockdown of Dmel\Epg5 in larval fat body result in phenotypes indicating a failure of the late phases of autophagic digestion and clearance; while adult eye-specific RNAi knockdown results in progressive loss of photoreceptor neurons in the retina. Similar phenotypes are observed in Dmel\Epg5; these flies also exhibit an age-related hyperthermia-inducible seizure phenotype. Physical interaction(s) of the Dmel\Epg5 protein have been described; see below and in the gene report for Epg5.
[updated Apr. 2025 by FlyBase; FBrf0222196]
[VICI SYNDROME; VICIS](https://omim.org/entry/242840)
[ECTOPIC P-GRANULES AUTOPHAGY PROTEIN 5 HOMOLOG; EPG5](https://omim.org/entry/615068)
Vici syndrome is a rare congenital multisystem disorder characterized by lack of development of the corpus callosum, cataracts, pigmentary defects, progressive cardiomyopathy, and variable immunodeficiency. Affected individuals also have profound psychomotor retardation and hypotonia due to a myopathy (summary by Finocchi et al., 2012; pubmed:21965116). [from MIM:242840; 2017.01.05]
Vici syndrome (VICIS) is caused by homozygous or compound heterozygous mutation in the EPG5 gene (autosomal recessive). [from MIM:242840; 2017.01.05]
Histological assessment of patient skeletal muscle tissue showed features of defective autophagy, including storage of abnormal material and secondary mitochondrial abnormalities (Cullup et al., 2013; pubmed:23222957). [from MIM:242840; 2017.01.05]
The product of the EPG5 gene is involved in autophagy; it may play a role in a late step of autophagy, such as clearance of autophagosomal cargo. [from Gene Cards, EPG5; 2017.01.05]
One to one: 1 human to 1 Drosophila.
High-scoring ortholog of human EPG5 (1 Drosophila to 1 human). Dmel\Epg5 shares 24% identity and 42% similarity with human EPG5.
