Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla; CIBERNED, Seville, Spain.
Molecular Genetics Section, Laboratory of Neurogenetics, NIA, NIH, Bethesda, MD, USA.
Neurobiol Aging. 2021 Jan;97:144.e1-144.e3. doi: 10.1016/j.neurobiolaging.2020.07.003. Epub 2020 Jul 14.
Genetic variation within the mitochondrial pathway contributes to the risk of Parkinson's disease (PD). Recent genetic analyses have investigated the association between the RHOT1 and RHOT2 genes and PD etiology. Furthermore, 4 mutations in the RHOT1 gene (p.R272Q, p.R450C, p.T351A, p.T610A) have been reported to be potentially associated with disease risk. As part of the International Parkinson Disease Genomics Consortium efforts to evaluate reported PD risk factors, we assessed the role of common and low frequency variants in both RHOT1 and also RHOT2 according to the high degree of homology in their amino acid sequences. Utilizing large-scale genotyping and whole-genome sequencing data from the International Parkinson Disease Genomics Consortium and the Accelerating Medicines Partnership - Parkinson Disease initiative, our analyses did not identify evidence to support the hypothesis that RHOT1 and RHOT2 are disease causing or modifying genes for PD risk or age at onset.
线粒体途径中的遗传变异导致帕金森病（PD）的风险增加。最近的遗传分析研究了 RHOT1 和 RHOT2 基因与 PD 病因之间的关联。此外，已经报道了 RHOT1 基因中的 4 种突变（p.R272Q、p.R450C、p.T351A、p.T610A）与疾病风险潜在相关。作为国际帕金森病基因组学联合会评估报告的 PD 风险因素的一部分，我们根据其氨基酸序列的高度同源性，评估了 RHOT1 和 RHOT2 中常见和低频变体的作用。利用国际帕金森病基因组学联合会和加速药物研发合作组织-帕金森病倡议的大规模基因分型和全基因组测序数据，我们的分析没有发现证据支持 RHOT1 和 RHOT2 是导致 PD 风险或发病年龄的致病或修饰基因的假设。
