A genetic cluster of early onset Parkinson's disease in a Colombian population

Abstract

We previously identified in two families with early onset Parkinson's Disease (PD) from the isolated population of Antioquia (Colombia), a parkin Cys212Tyr substitution caused by a G736A mutation. This mutation was subsequently observed in a Spanish family, suggesting that it could have been taken to Antioquia by Spanish immigrants. Here we screened for the G736A mutation in additional Antioquian early onset PD cases and used haplotype analysis to investigate the relationship between Spanish and Antioquian G736A chromosomes. We confirmed the occurrence of an extensive founder effect in Antioquia. Thirteen individuals (10 homozygotes) from seven nuclear families were identified with the G736A mutation. Genealogical investigations demonstrated the existence of shared ancestors between six of these families four to five generations ago and no evidence of Spanish ancestry during this period. A second parkin mutation (a duplication of exon 3), was detected in the three G736A heterozygote carriers. Haplotype data exclude a recent common ancestry between the Spanish and Antioquian patients studied here and is consistent with the introduction of the G736A mutation in Antioquia during early colonial times (about 16 generations ago).

Life Span and Locomotor Activity Modification by Glucose and Polyphenols in Drosophila melanogaster Chronically Exposed to Oxidative Stress-stimuli: Implications in Parkinson’s Disease

“…Therefore, by using Ddc-GAL4 Drosophila melanogaster line, (3) we also investigated whether genetically altered Ddc-GAL4 flies renders them sensitive to PQ-induced oxidative stress and (4) whether glucose and polyphenols might modulate life span and/or locomotor activity in this line of Drosophila melanogaster. Based on our present findings, we proposed that a combined therapy with antioxidant and high energetic agents should provide to pre-clinical genetically individuals at risk to suffer PD a means to delay or to prevent motor symptoms and/or frank PD, as those encounter in Antioquia, Colombia [36]. These data may contribute to a better understanding of the inherent nutritional status, genetic predisposition and environmental agents as causative factors of PD.…”

Variants in triggering receptor expressed on myeloid cells 2 are associated with both behavioral variant frontotemporal lobar degeneration and Alzheimer's disease

“…Rare Mendelian disease in isolated populations is almost always attributable to a single mutation that is shared identical-by-descent among affected individuals in the population. In the Antioquia population, founder mutations have been identified previously, for example, the c.G736A mutation in the PARK2 gene that causes early onset Parkinson’s Disease (Pineda-Trujillo et al, 2006). It is unclear however when the p.Trp198X TREM2 mutation arose in Antioquia.…”

Novel MLH1 duplication identified in Colombian families with Lynch syndrome

“…The Antioquia area in Colombia is a population isolate where founder effects have been previously detected for other hereditary conditions such as Alzheimer or Parkinson disease. 29,30 Therefore, it may be recommended to prescreen MLH1ϪLS Antioquia families for this putative founder mutation before performing the thorough MMR mutational screening.…”