Early-Onset Parkinson Disease Screening in Patients From Nigeria

Lukasz Milanowski

Olajumoke Oshinaike

Benjamin Broadway

Jennifer Lindemann

Alexandra Soto-Beasley

Ronald Walton

Rana Al-Shaikh

Audrey Strongosky

Fabienne Fiesel+4 authors

^{Department of Neurology, Mayo Clinic Florida, Jacksonville, FL, United States}

^{Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, United States}

^{Department of Neurology, Lagos State University Teaching Hospital, Lagos, Nigeria}

^{Neuroscience PhD Program, Mayo Clinic Graduate School of Biomedical Sciences, Jacksonville, FL, United States}

^{Department of Clinical Genomics, Mayo Clinic Florida, Jacksonville, FL, United States}

Edited by: Ignacio Mata, Cleveland Clinic, United States

Reviewed by: Suzanne Lesage, Institut National de la Santé et de la Recherche Médicale (INSERM), France; Luca Marsili, University of Cincinnati, United States

*Correspondence: Wolfdieter Springer ude.oyam@reteidfloW.regnirpS

Shamsideen Abayomi Ogun moc.oohay@2002nugoimoy

Zbigniew K. Wszolek ude.oyam@weingibZ.kelozsW

This article was submitted to Neurogenetics, a section of the journal Frontiers in Neurology

†ORCID: Lukasz M. Milanowski orcid.org/0000-0003-4197-8518

Benjamin J. Broadway orcid.org/0000-0002-1260-6910

Fabienne C. Fiesel orcid.org/0000-0002-1919-9676

Wolfdieter Springer orcid.org/0000-0002-1178-3149

‡These authors have contributed equally to this work

Edited by: Ignacio Mata, Cleveland Clinic, United States

Reviewed by: Suzanne Lesage, Institut National de la Santé et de la Recherche Médicale (INSERM), France; Luca Marsili, University of Cincinnati, United States

Received 2020 Aug 14; Accepted 2020 Nov 25.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Abstract

Introduction: 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 PRKN, PINK1, DJ1, SNCA multiplication, and LRRK2 p.G2019S.

Methods: 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 <50 years). All patients with EOPD were sequenced for the coding regions of PRKN, PINK1, and DJ1. Exon dosage analysis was performed with a multiplex ligation-dependent probe amplification assay, which also included a SNCA 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.

Results: In 15 patients with EOPD, 22 variants were observed [PRKN, 9 (40.9%); PINK1, 10 (45.5%); and DJ1, 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 SNCA genomic multiplications or LRRK2 p.G2019S were identified. The PINK1 p.R501Q functional analysis revealed pathogenic loss of function.

Conclusion: 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.

Keywords: Nigerian population, MLPA, Sanger sequencing, LRRK2, PRKN, PINK1, DJ1, Parkinson disease

Abstract

Footnotes

Funding. Mayo Clinic is an American Parkinson Disease Association (APDA) Mayo Clinic Information and Referral Center, an APDA Center for Advanced Research and the Mayo Clinic Lewy Body Dementia Association (LBDA) Research Center of Excellence. LM is supported by the Polish National Agency for Academic Exchange Iwanowska's Fellowship PPN/IWA/2018/1/00006/U/00001/01, the APDA and the Haworth Family Professorship in Neurodegenerative Diseases fund. OR is supported by the National Institutes of Health (NIH; R01 NS078086; U54 NS100693; U54 NS110435), the US Department of Defense (W81XWH-17-1-0249), The Little Family Foundation, Mayo Clinic Functional Genomics of LBD Program, the Mayo Clinic Center for Individualized Medicine, and the Michael J. Fox Foundation for Parkinson's Research (MJFF). FF was the recipient of fellowships from the Younkin Scholar Program and the APDA and was supported in part by the MJFF (15625) and a Gerstner Family Career Development Award from the Mayo Clinic Center for Individualized Medicine (CIM). WS was partially supported by the National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke (NINDS) (RF1 NS085070, R01 NS110085, and U54 NS110435), National Institute on Aging (NIA) (R56 AG062556), the Department of Defense Congressionally Directed Medical Research Programs (CDMRP) (W81XWH-17-1-0248), the Florida Department of Health - Ed and Ethel Moore Alzheimer's Disease Research Program (9AZ10) the MJFF (15007), Mayo Clinic Foundation and the Center for Biomedical Discovery (CBD). ZW is partially supported by the Mayo Clinic Center for Regenerative Medicine, gifts from The Sol Goldman Charitable Trust and the Donald G. and Jodi P. Heeringa Family, the Haworth Family Professorship in Neurodegenerative Diseases fund, and The Albertson Parkinson's Research Foundation. He serves as PI or Co-PI on grants from Biogen, Inc. (228PD201), and Biohaven Pharmaceuticals, Inc. (BHV4157-206 and BHV3241-301), and Neuraly, Inc. (NLY01-PD-1). He serves as Co-PI of the Mayo Clinic APDA Center for Advanced Research.

Footnotes

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