Analysis of Nigerians with Apparently Sporadic Parkinson Disease for Mutations in LRRK2, PRKN and ATXN3

Njideka Okubadejo,Jose Bras,Angela Britton,Rufus Akinyemi,John Hardy,Andrew Singleton,Cynthia Crews,Amanda Ewart Toland

doi:10.1371/journal.pone.0003421

Abstract

Several genetic variations have been associated with Parkinson disease in different populations over the past few years. Although a considerable number of worldwide populations have been screened for these variants, results from Sub-Saharan populations are very scarce in the literature. In the present report we have screened a cohort of Parkinson disease patients (n = 57) and healthy controls (n = 51) from Nigeria for mutations in the genes PRKN, LRRK2 and ATXN3. No pathogenic mutations were found in any of the genes. Hence, common pathogenic mutations in these genes, observed in several different populations, are not a frequent cause of Parkinson disease in Nigeria.

Highlights

The identification of monogenic causes of Parkinson’s disease (PD) (MIM #168600) has improved our understanding of the pathogenesis of the disease and promises to facilitate the development of biomarkers to aid early diagnosis and interventions that may slow disease progression or even provide a cure in the future
Samples that showed only one heterozygous mutation in PRKN that was not present in controls were screened for copy number variants in this gene, in order to assess if these were compound heterozygous for one point and one genomic copy number mutation
Genomic copy number analysis did not detect any mutations in these samples. This is the first study screening a sub-Saharan African cohort of apparently sporadic PD cases for mutations in genes commonly associated with PD

Summary

Introduction

The identification of monogenic causes of Parkinson’s disease (PD) (MIM #168600) has improved our understanding of the pathogenesis of the disease and promises to facilitate the development of biomarkers to aid early diagnosis and interventions that may slow disease progression or even provide a cure in the future. Mutations in two genes have been linked to autosomal dominant PD; the first, encoding a-synuclein (SNCA; MIM #163890; PARK1) [1] and the second encoding leucine-rich repeat kinase 2 (LRRK2; MIM #609007; PARK8) [2,3]. Pathogenic repeat expansion mutations in the genes encoding ataxin-3 (ATXN3; MIM #109150) [7] and ataxin-2 (ATXN2; MIM #183090) [8] have been described as autosomal dominant causes of PD. Heterozygous mutations are fairly common in healthy subjects [13], and second, the presence of an apparent single heterozygous mutation in a PD patient typically should not rule out PRKN as the causative gene, since other unscreened mutations may be present [16]

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Conclusion