This report describes Parkinsonism with polyneuropathy (PKNPY); PKNPY exhibits autosomal dominant inheritance. The human gene implicated in this disease is UQCRC1, which encodes a component of the mitochondrial respiratory chain complex III. There is a single orthologous gene in Drosophila, UQCR-C1; UQCR-C1 is also closely related to the human gene PMPCB. Multiple genetic reagents including RNAi-targeting constructs, an allele caused by insertional mutagenesis, and a CRISPR/Cas9-generated amorphic mutation have been generated for Dmel\UQCR-C1.
Multiple UAS constructs of human Hsap\UQCRC1 have been introduced into flies, including wild-type and a variant implicated in this disease. See the 'Disease-Implicated Variants' table, below.
Assayed in a heterozygous Dmel\UQCR-C1 genotype and compared to expression of the wild-type human gene, pan-neuronal expression of the Hsap\UQCRC1 Y314S variant causes age-dependent locomotor impairment and decreased lifespan; significant loss of dopaminergic neurons in older adult brains is observed. Phenotypes observed in larval neuromuscular junctions (NMJs) suggest pre-synaptic nerve defects are associated with expression of the Y314S variant.
[updated Aug. 2021 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]
[PARKINSONISM WITH POLYNEUROPATHY; PKNPY](https://omim.org/entry/619279)
[UBIQUINOL-CYTOCHROME c REDUCTASE CORE PROTEIN I; UQCRC1](https://omim.org/entry/191328)
Parkinsonism with polyneuropathy (PKNPY) is an autosomal dominant disorder characterized by asymmetrical tremor-dependent parkinsonism. The age of onset ranges from the late forties to mid-sixties, and patients have a good response to levodopa (summary by Lin et al., 2020; pubmed:33141179). [from MIM:619279; 2021.04.27]
Individuals from multiple families with autosomal dominant late-onset Parkinson disease have been shown to carry rare variants in the UQCRC1 gene (FBrf0247429).
Parkinsonism with polyneuropathy (PKNPY) is caused by heterozygous mutation in the UQCRC1 gene. [from MIM:619279; 2021.04.27]
UQCRC1 encodes a component of the ubiquinol-cytochrome c oxidoreductase transmembrane complex (complex III) that is part of the mitochondrial electron transport chain which drives oxidative phosphorylation.
Many to one: 2 human genes to Drosophila gene; the second human gene is PMPCB.
Moderate- to high-scoring ortholog of human PMPCB and UQCRC1 (1 Drosophila to 2 human). Dmel\UQCR-C1 shares 57-66% identity and 75-76% similarity with the human genes.
