This is the first study screening a sub-Saharan African cohort of apparently sporadic PD cases for mutations in genes commonly associated with PD. The results from this study are of clear importance not only for Nigerian PD patients, but also because they shed light on the genetic background associated with PD in the African population. It should be noted that the number of individuals included in this preliminary report is clearly small, and thus, definite conclusions about frequencies of variants are difficult to achieve.
We have performed a screening for the most common autosomal recessive variants in three genes associated with PD (LRRK2
). We decided not to screen for mutations in the genes PINK1
given the low frequency of mutations in these genes in worldwide populations. Moreover, we did not screen SNCA
as mutations in this gene are not only rare but they are also associated with an autosomal dominant mode of inheritance. Given that the majority of our patients have no affected family members with any form of parkinsonism, mutations in SNCA
would be unlikely to occur in our cohort. Mutations in the LRRK2
are the most common cause of PD in several populations, including populations of Northern-African ancestry. In particular, Lesage and colleagues found a high frequency (41%) of the G2019S mutation on exon 41 in a study of North African Arabs that included both familial and apparently sporadic PD cases 
. Thus, it would be interesting to determine if there is a similarly high frequency of LRRK2
G2019S mutations in other geographically and ethnically distinct parts of Africa. However, we did not find any mutations in either exons 31 and 41 of LRRK2
in our cohort, suggesting that mutations in these domains of LRRK2
are not a common cause of PD in sub-Saharan populations. A recent study performed a comprehensive analysis of the entire coding region of LRRK2
in a large cohort of American PD cases and healthy controls 
. Of the seven mutations found to be segregating with disease, five were in either exon 31 or exon 41, indicating these as clear mutational hotspots. The noteworthy difference in mutation frequency among populations from the same continent is, in all probability, due to the occurrence of the founding G2019S mutation event happening after human populations moved out of sub-Saharan Africa as this is most consistent with the dating of this mutational event 
Parkinsonism due to ATXN3 repeat expansion mutation has been previously described in one single large African descent family. We failed to find any samples harboring the increased repeat expansion size. This result suggests that ATXN3 repeat expansion mutations are not a frequent cause of parkinsonism in this population.
Even though a considerable number of PRKN
mutations are dosage mutations, the majority are sequence variants, hence, we decided to perform the initial screen of our cohort only for these variants. Subsequently, we performed gene dosage analysis in two samples as previously detailed. Again, our study did not identify any pathogenic mutations in PRKN
in our subset of PD patients. We found several heterozygous variants both in patients and controls.,Two of the variants are novel and present only in PD cases (p.R334H and p.A46T). Given the fact that these are novel variants, we ran the analysis software SIFT (available at http://blocks.fhcrc.org/sift/
in order to have some insight into the potential effects of these variants. The p.A46T was predicted by the software to potentially affect protein function, whereas the p.R334H was predicted to have no functional effect. However, these results are merely based on a similarity score in comparison to other proteins, and hence it must be stressed that this is not true functional data for these variants. Nonetheless, in the absence of a second mutation, these cannot be described as pathogenic, thus we decided to classify these as variants of unknown pathogenicity. It should be noted that for these two samples, an additional screen for gene dosage mutations was performed using the Illumina BeadChips. In addition, one homozygous variant was found only in the PD group (p.S167N; c.G500A). However, this has previously been classified as a polymorphism 
All populations showed polymorphisms with varying frequencies. Three variants p.A46T, p.P153R and p.R334H were found in a single sample each. Variant p.A46T was present in one PD sample from Igbo, p.P153R was found in a Yoruban sample, and p.R334H was present in a sample with Edo background. Two individuals, both from the same ethnic region (Edo), presented with two missense variants each (p.M129L and p.S167N; p.M129L and p.V380L). Although the present study cannot completely rule out that these compound hetererozygous events could potentially be pathogenic, two facts suggest otherwise: 1) in each case the second variant is a well known and described SNP; 2) one control sample presented the same combination of two of the variants (p.M129L and p.V380L).
We report the first genetic screening for PD genes in a sub-Saharan population. We found no pathogenic mutations in the genes most commonly known to cause PD in European North American, or North African populations. Although the cohort studied is clearly small and definite conclusions regarding frequencies are unachievable, a trend for different genetic basis of PD in this sub-Saharan population is, in our opinion, noteworthy. Two main caveats are present in this work: gene dosage mutations in PRKN were only screened for in two samples and only exons 31 and 41 of LRRK2 were sequenced. Nevertheless, the aim of this study was to ascertain a preliminary frequency of the most common variants known to cause PD in a sub-Saharan population. We report here that the most common variant associated with PD in several world-wide populations, the p.G2019S mutation in LRRK2, is not overrepresented in this Nigerian population of PD patients; similarly, sequence variants in PRKN, which represent a significant proportion of PRKN mutations underlying PD, are also not significantly present in the studied cohort. It is thus likely that the differences in the genetic background of these populations mean that other genes or different variants are underlying the disease. Therefore, a search for these is clearly warranted, since they will, in all probability, shed more light on different pathways leading to PD.