Assuntos
Doença de Parkinson/etnologia , Doença de Parkinson/genética , Polimorfismo de Nucleotídeo Único/genética , Proteínas Serina-Treonina Quinases/genética , População Negra , Estudos de Casos e Controles , Feminino , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Masculino , África do Sul , População BrancaRESUMO
The R1205H mutation in the eukaryotic translation initiation factor 4G1 (EIF4G1) gene and the D620N mutation in the vacuolar protein sorting 35 (VPS35) gene were recently found in patients with autosomal dominant or sporadic forms of Parkinson's disease (PD). In the present study, 418 South African PD patients and 528 control subjects of diverse ethnicities were screened using the KASP (Kompetitive Allele Specific PCR) genotyping assay. The mutations were not found in our study, suggesting that they are not a common cause of PD in South African patients. Further studies are needed on the frequency of these 2 mutations in other sub-Saharan African populations.
Assuntos
Fator de Iniciação Eucariótico 4G/genética , Taxa de Mutação , Mutação/genética , Transtornos Parkinsonianos/etnologia , Transtornos Parkinsonianos/genética , Proteínas de Transporte Vesicular/genética , Suscetibilidade a Doenças , Técnicas de Genotipagem , Humanos , África do Sul/etnologiaRESUMO
Parkinson's disease (PD) is under-studied in Black Sub-Saharan African (SSA) populations. To date, there have been only six prevalence and no incidence studies. The crude prevalence of PD in SSA varies from 7 to 20 per 100,000, which is appreciably lower than in Caucasian populations. There are a limited number of published studies (nine) on the genetic factors associated with PD in SSA populations. Mutations have been reported in the parkin gene, and are restricted to only three patients (two Black South Africans and one Zambian). No mutations have been identified in the LRRK2, SNCA, PINK, or DJ-1 genes. Given the unique ancestry of SSA populations, their inclusion in genetic studies may provide a substantial contribution to the identification of novel genetic factors and genetic-environmental interactions underlying this disorder. More initiatives are needed to drive further research on PD in these populations and to facilitate collaborative projects across Africa.
Assuntos
Doença de Parkinson/epidemiologia , Doença de Parkinson/genética , Ubiquitina-Proteína Ligases/genética , África Subsaariana/epidemiologia , Estudos de Associação Genética , Humanos , PrevalênciaRESUMO
The molecular basis of Parkinson's disease (PD) has been extensively studied in numerous population groups over the past decade. However, very little is known of the molecular etiology of PD in the South African population. We aimed to assess the genetic contribution of parkin mutations to PD pathology by determining the frequency of both point mutations and exon rearrangements in all 12 exons of the parkin gene in a group of 229 South African patients diagnosed with PD. This was done by performing high resolution melt (HRM) as well as multiplex ligation-dependent probe amplification (MLPA) analyses. In total, seven patients (3.1%; 7/229) had either compound heterozygous or homozygous mutations in parkin, and seven patients (3.1%) had heterozygous sequence variants. Two of the patients with parkin mutations are of Black African ancestry. Reverse-transcription PCR on lymphocytes obtained from two patients verified the presence of parkin mutations on both alleles. In conclusion, the present study reveals that mutations in the parkin gene are not a major contributor to PD in the South African population. Further investigations of the molecular etiology of PD in the unique South African population, particularly the Black African and mixed ancestry sub-populations, are warranted.