AUTHOR=Milanowski Lukasz M. , Oshinaike Olajumoke , Broadway Benjamin J. , Lindemann Jennifer A. , Soto-Beasley Alexandra I. , Walton Ronald L. , Hanna Al-Shaikh Rana , Strongosky Audrey J. , Fiesel Fabienne C. , Ross Owen A. , Springer Wolfdieter , Ogun Shamsideen Abayomi , Wszolek Zbigniew K. 

TITLE=Early-Onset Parkinson Disease Screening in Patients From Nigeria

JOURNAL=Frontiers in Neurology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2020.594927

DOI=10.3389/fneur.2020.594927

ISSN=1664-2295

ABSTRACT=<p><bold>Introduction:</bold> Nigeria is one of the most populated countries in the world; however, there is a scarcity of studies in patients with age-related neurodegenerative diseases, such as Parkinson disease (PD). The aim of this study was to screen patients with PD including a small cohort of early-onset PD (EOPD) cases from Nigeria for <italic>PRKN, PINK1, DJ1, SNCA</italic> multiplication, and LRRK2 p.G2019S.</p><p><bold>Methods:</bold> We assembled a cohort of 109 Nigerian patients with PD from the four main Nigerian tribes: Yoruba, Igbo, Edo, and Hausa. Fifteen cases [14 from the Yoruba tribe (93.3%)] had EOPD (defined as age-at-onset &lt;50 years). All patients with EOPD were sequenced for the coding regions of <italic>PRKN, PINK1</italic>, and <italic>DJ1</italic>. Exon dosage analysis was performed with a multiplex ligation-dependent probe amplification assay, which also included a <italic>SNCA</italic> probe and LRRK2 p.G2019S. We screened for LRRK2 p.G2019S in the entire PD cohort using a genotyping assay. The PINK1 p.R501Q functional analysis was conducted.</p><p><bold>Results:</bold> In 15 patients with EOPD, 22 variants were observed [<italic>PRKN</italic>, 9 (40.9%); <italic>PINK1</italic>, 10 (45.5%); and <italic>DJ1</italic>, 3 (13.6%)]. Three (13.6%) rare, nonsynonymous variants were identified, but no homozygous or compound heterozygous carriers were found. No exonic rearrangements were present in the three genes, and no carriers of <italic>SNCA</italic> genomic multiplications or LRRK2 p.G2019S were identified. The PINK1 p.R501Q functional analysis revealed pathogenic loss of function.</p><p><bold>Conclusion:</bold> More studies on age-related neurodegenerative diseases are needed in sub-Saharan African countries, including Nigeria. Population-specific variation may provide insight into the genes involved in PD in the local population but may also contribute to larger studiesperformed in White and Asian populations.</p>