In a genome-wide study, association was found between CNVs in the PARK2 gene and autism in AGRE and ACC cohorts (European ancestry) (Glessner et al., 2009). In addition, a rare duplication in the PARK2 gene has been identified in an individual with ASD (Oâ??Roak et al., 2012). As well, rare variants in the PARK2 gene have been identified in individuals with autosomal recessive juvenile parkinsonism (Kitada et al., 1998).
Type of Disorder
Autism genome-wide copy number variation reveals ubiquitin and neuronal genes.
In the paper by Glessner et al. (2009) there were 7 deletions observed in cases (discovery and replication datasets) and 0 in controls. 1/7 variants were confirmed by qPCR, but the status of the remainder is unknown (P value of 3.3 x 10-3 is for genes within GO term ?ubiquitin conjugation?, not PARK2 alone). Gene-level statistical support is only nominal. The variants are all inherited and so are incompletely penetrant. OMIM indicates that autosomal recessive mutations result in juvenile onset Parkinson?s disease.
Category 4 - Minimal Evidence
Genes with a series of two or more putative mutations identified (e.g. non-synonymous substitutions, single-gene deletion, duplication, disruption by translocation) for which there is not rigorous statistical comparison with controls.
Model Genotype: Homozygous
Mutation: Targeted deletion of parkin exon 3 resulting in frameshift after amino acid 57 of parkin
Allele Type: Targeted (Knock Out)
Strain of Origin: 129Sv/J
Genetic Background: C57BL/6
ES Cell Line: R1
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Description: Decreased mitochondrial respiration of Complex I in the presence of the uncouple CCCP Exp Paradigm: Mitochondria measurement of respiration in slices of Substantia nigra in the presence of CCCP
Description: Abnromal brain ultrastructure characterized by abnormal mitochondria and lipfouscin granules within dopaminergic neurons in the Substantia Nigra Exp Paradigm: Electron microscopy with immunogold technique in the substantia nigra
Description: Abnormal brain ultrastructure characterized by cytoplasmic vacuoles, disruption of golgi network, endoplasmic reticulum, abnormal mitochondria - electron dense inclusion bodies, dilated and disorganzied cristae Exp Paradigm: Electron microscopy of the Substantia Nigra, the striatum, and the Cortex