Clinical Findings and Genetic Screening for Copy Number Variation Mutations in a Cohort of South African Patients with Parkinson's Disease

ABSTRACT

BACKGROUND:Parkinson's disease (PD); with a prevalence of up to 4% in Western countries; appears to be less common in Africa; possibly in part because of genetic factors. African studies investigating the genetic causation of PD are limited. OBJECTIVE:To describe the clinical and genetic findings in a group of black South African patients with PD.METHODS:All black African patients with PD from a tertiary hospital neurology clinic were examined. Symptoms were scored according to the Unified Parkinson's Disease Rating Scale (UPDRS); and patients were classified according to motor features. Genomic DNA was extracted and multiplex ligation-dependent probe amplification was used for detection of copy number variation (CNV) mutations in the known PD-causing genes.RESULTS:Sixteen patients were identified (ages 56 - 82 years). Three had a family history of PD. Classification into motor subtypes showed 44% mixed; 31% akinetic-rigid; and 25% tremor-dominant subtypes. UPDRS scores ranged from 7 to 88; with dementia in 20%. No patient had G2019S LRRK2 and A30P SNCA mutations; and all except one had no CNV mutations in the known PD-causing genes. A female patient (age of onset 50 years; no family history) had a parkin gene heterozygous deletion of exon 4. She had hyperreflexia; bilateral Hoffmann's reflexes; normal plantar responses and no dystonia.CONCLUSION:This group of black African patients showed similar characteristics to patients in Western studies; possibly with a higher proportion having tremor-dominant disease. Genetic analysis showed one parkin gene mutation. The limited knowledge on PD-causing genes and mutations in black populations warrants further studies involving next-generation sequencing approaches