This report describes Parkinson disease 23 (PARK23), which is an early-onset subtype of Parkinson disease; PARK23 exhibits autosomal recessive inheritance. The human gene implicated in this disease is VPS13C (Vacuolar Protein Sorting 13 Homolog C), which is necessary for proper mitochondrial function and maintenance of mitochondrial transmembrane potential. The most closely related gene in Drosophila is Vps13, which is also orthologous to the human gene VPS13A. VPS13A is implicated in chorea-acanthocytosis (see FBhh0000592). There are additional members of the VPS family in both species. RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated for Dmel\Vps13
The human VPS13C gene has not been introduced into flies.
RNAi-mediated knockdown of Vps13 enhances neurodegeneration phenotypes observed for a fly genotype representing a model of Parkinson disease 1 model (FBrf0234618). For information and links concerning disease model experiments using the fly gene Vps13, see 'neurodegenerative disease, VPS13-related' (FBhh0000625).
[updated Jul. 2019 by FlyBase; FBrf0222196]
Parkinson disease (PD) is a neurodegenerative disease usually typified by slow onset in mid to late adulthood; there are also early-onset and juvenile forms of the disease. Symptoms worsen over time and include resting tremor, muscular rigidity, bradykinesia [abnormal slowness of movement], and postural instability [impaired balance and coordination]; additional symptoms may include postural abnormalities, dysautonomia [symptoms caused by malfunction of the autonomic nervous system], dystonic cramps, and dementia. Parkinson disease is the second-most common neurodegenerative disease (after Alzheimer disease), affecting approximately 1% of the population over 50 (Polymeropoulos et al., 1996, pubmed:8895469). [from MIM:168600; 2013.07.23]
Parkinson disease is described as early-onset disease if signs and symptoms begin before age 50. Early-onset cases that begin before age 20 may be referred to as juvenile-onset disease. [from Genetics Home Reference, GHR_condition:parkinson-disease, 2015.02.13]
[PARKINSON DISEASE 23, AUTOSOMAL RECESSIVE EARLY-ONSET; PARK23](https://omim.org/entry/616840)
[VACUOLAR PROTEIN SORTING 13 HOMOLOG C; VPS13C](https://omim.org/entry/608879)
Based on 3 patients: onset of rapidly progressive Parkinson disease between 25 and 46 years of age. Early in the disease, the patients showed typical signs of the disorder, including a kineto-rigid syndrome, resting tremor, and good response to levodopa. However, the disease progressed rapidly with progressive cognitive impairment leading to dementia and dysautonomia; patients became bedridden within 15 years of onset (Lesage et al., 2016; pubmed:26942284). [from MIM:616840; 2017.09.21]
Autosomal recessive early-onset Parkinson disease-23 (PARK23) is caused by homozygous or compound heterozygous mutation in the VPS13C gene. [from MIM:616840; 2017.09.21]
In cellular studies, Lesage et al. (2016; pubmed:26942284) found that knockdown of VPS13C resulted in perinuclear redistribution of mitochondria and mitochondrial fragmentation and was associated with a decrease in mitochondrial transmembrane potential. [from MIM:608879; 2017.09.21]
VPS13C encodes a vacuolar protein sorting-associated protein which is necessary for proper mitochondrial function and maintenance of mitochondrial transmembrane potential. [Gene Cards, VPS13C; 2017.09.22]
Many to one: 2 human to 1 Drosophila; other lower-scoring orthologs in both species. The second human gene is VPS13A.
