This report describes chorea-acanthocytosis, also called choreoacanthocytosis (ChAc or CHAC); ChAc exhibits autosomal recessive inheritance. The gene implicated in this disease is VPS13A, (Vacuolar Protein Sorting 13 Homolog A ), a gene conserved from yeast to human. Based on work in yeast, it is postulated to be involved in proper intracellular trafficking of proteins through the trans-Golgi network. There is a single orthologous gene in flies, Dmel\Vps13, for which RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated. There are additional members of the VPS family in both species. Dmel\Vps13 is also closely related to the human gene VPS13C, which has been implicated in Parkinson disease 23 (FBhh0000624).
A UAS construct of the wild-type human Hsap\VPS13A gene has been introduced into flies. Partial heterologous rescue (functional complementation) of the Dmel\Vps13 loss-of-function phenotypes is observed.
For information and links concerning disease model experiments using the fly gene Vps13, see 'neurodegenerative disease, VPS13-related' (FBhh0000625).
[updated Sep. 2017 by FlyBase; FBrf0222196]
[CHOREOACANTHOCYTOSIS; CHAC](https://omim.org/entry/200150)
[VACUOLAR PROTEIN SORTING 13 HOMOLOG A; VPS13A](https://omim.org/entry/605978)
Chorea-acanthocytosis is primarily a neurological disorder; common symptoms include chorea (involuntary jerking movements), dystonia (involuntary muscle contractions, spasms), tics, impaired speech, and progressive cognitive impairment; behavioral and personality changes are common early symptoms. [Genetics Home Reference, chorea-acanthocytosis; 2017.08.04]
Choreoacanthocytosis (CHAC) is a rare disorder characterized by progressive neurodegeneration and red cell acanthocytosis, with onset in the third to fifth decade of life (Rubio et al., 1997; pubmed:9382101). [from MIM:200150; 2017.08.04]
Choreoacanthocytosis can be caused by homozygous or compound heterozygous mutation in the VPS13A gene. [from MIM:200150; 2017.08.04]
Some red blood cells are abnormal, having multiple spiny cytoplasmic projections (acanthocytosis); they may described as thorny or as star-shaped. [Genetics Home Reference, chorea-acanthocytosis; 2017.08.04]
Acanthocytes are present in 5%-50% of the red cell population. In some cases, acanthocytosis may be absent or may appear only late in the course of the disease. The proportion of acanthocytes does not correlate with disease severity. [from Gene Reviews, Chorea-Acanthocytosis; 2017.08.07]
Based on work done characterizing the orthologous gene in yeast, VPS13A (originally designated chorein) is required for proper intracellular trafficking of certain proteins through the trans-Golgi network to early and late endosomes, lysosomes, and the plasma membrane. [from Gene Reviews, Chorea-Acanthocytosis; 2017.08.07]
Many to one: 2 human to 1 Drosophila; other lower-scoring orthologs in both species. The second human gene is VPS13C.
