Rare heterozygous parkin variants in French early-onset Parkinson disease patients and controls

Abstract

These results suggest that single parkin mutations increase the risk of early-onset PD, but the possibility of a second parkin mutation cannot be excluded.

A comprehensive analysis of deletions, multiplications, and copy number variations in PARK2

“…[10][11][12][13][14]16,17 However, not all studies found a higher frequency in patients than in controls. 20 Although the sampling of patients varied across studies (early-onset, late-onset, familial PD), the frequency of PARK2 mutations in our patients with PD, when subgrouped to match each study, are generally in line with most prior studies.…”

“…The majority of positive results are heterozygous and difficult for clinicians to interpret because whether having one mutation can cause, increase risk, or accelerate onset of Parkinson disease (PD) is unknown. [9][10][11][12][13][14][15][16][17][18][19][20][21] The second aim of our study was to determine, conclusively, if heterozygous mutations are associated with PD. We designed this study specifically to address this question, and to that end, amassed a large sample size to ensure analytic power, analyzed the coding regions for all types of variations, and importantly, used the same rigorous mutation analysis and validation methods in control subjects as in patients.…”

Epidemiology and etiology of Parkinson’s disease: a review of the evidence

“…Several studies found earlier age of onset in individuals with two compared to those with only one Parkin mutation [223,227,228]. Parkin is an E3 ubiquitin ligase with several substrates, one being the glycosylated form of α-Synuclein [229].…”

Four novel C20orf54 mutations identified in Brown–Vialetto–Van Laere syndrome patients

“…18,19,22,23 The possibility that a single mutated allele in a gene can be cause of disease when usually two mutated alleles are causative has been considered for some neurologic disorders, such as for Parkinson's disease with respect to PARKN and for some myopathies such as limb-girdle muscular dystrophy with respect to TTN. [24][25][26][27] The case of SOD1 mutations with respect to amyotrophic lateral sclerosis, which like BVVLS is a motor neuron disorder, is also interesting. SOD1 mutations are usually observed in amyotrophic lateral sclerosis families that exhibit autosomal dominant inheritance.…”