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
Department of Neurology, Mayo Clinic Florida, Jacksonville, FL, United States.
Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, United States.
Front Neurol. 2021 Jan 14;11:594927. doi: 10.3389/fneur.2020.594927. eCollection 2020.
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 multiplication, and LRRK2 p.G2019S. 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 , and . Exon dosage analysis was performed with a multiplex ligation-dependent probe amplification assay, which also included a 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. In 15 patients with EOPD, 22 variants were observed [, 9 (40.9%); , 10 (45.5%); and , 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 genomic multiplications or LRRK2 p.G2019S were identified. The PINK1 p.R501Q functional analysis revealed pathogenic loss of function. 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.
尼日利亚是世界上人口最多的国家之一；然而，针对年龄相关性神经退行性疾病患者，如帕金森病（PD）的研究却很匮乏。本研究的目的是对尼日利亚的帕金森病患者进行筛查，包括一小群早发性帕金森病（EOPD）病例，以检测基因倍增情况以及LRRK2基因p.G2019S突变。我们从尼日利亚四个主要部落（约鲁巴族、伊博族、江户族和豪萨族）招募了109名尼日利亚帕金森病患者组成队列。15例患者（14例来自约鲁巴族，占93.3%）患有早发性帕金森病（定义为发病年龄<50岁）。所有早发性帕金森病患者均对基因的编码区进行测序。采用多重连接依赖探针扩增法进行外显子剂量分析，该方法还包括一个探针和LRRK2基因p.G2019S检测。我们使用基因分型检测法对整个帕金森病队列进行LRRK2基因p.G2019S筛查。进行了PINK1基因p.R501Q功能分析。在15例早发性帕金森病患者中，观察到22个变异（基因，9个，占40.9%；基因，10个，占45.5%；基因，3个，占13.6%）。鉴定出3个（13.6%）罕见的非同义变异，但未发现纯合或复合杂合携带者。这三个基因均未出现外显子重排，也未鉴定出基因倍增或LRRK2基因p.G
