Molecular genetics of arrhythmogenic right ventricular cardiomyopathy in South Africa

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable disorder characterised by progressive degeneration of the right ventricular myocardium, arrhythmias and an increased risk of sudden death at a young age. Fourteen chromosomal loci have been linked to ARVC and nine disease genes have been identified. Linkage analysis of a South African family was previously performed at ARVC loci 1 to 6. ARVC loci 1 to 5 were excluded as disease loci in this family based on lack of evidence for linkage. However, a peak lod score of 2.93 was obtained for the ARVC-6 locus which is highly suggestive of linkage. Subsequently another locus (ARVC-7) and five ARVC disease genes (ARVC loci 8 to 12) have been reported. The aim of this project was to identify the disease gene that causes ARVC in this family

Patient-Control Association Study of the Leucine-Rich Repeat Kinase 2 (LRRK2) Gene in South African Parkinson's Disease Patients

The leucine-rich repeat kinase 2 (LRRK2) gene is of interest to Parkinson's disease (PD) as it has been implicated in both familial and sporadic forms of the disorder.1 PD-susceptibility alleles in LRRK2 appear to be ethnic-specific with G2385R,2 R1628P3 and A419V4 identified in Asian populations, whereas M1646T is found in Caucasians.4 A haplotype protecting against development of PD is present in Chinese (N551K-R1398H)5 and Caucasians (N551K-R1398H-K1423K).4 Further studies are necessary to investigate the contribution of LRRK2 to PD-susceptibility in various populations worldwide.Department of HE and Training approved lis

Mutations in the parkin gene are a minor cause of Parkinson's disease in the South African population

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. (C) 2011 Elsevier Ltd. All rights reserved