Kamath Sneha D, Phulpagar Prashant, Holla Vikram V, Kamble Nitish, Yadav Ravi, Muthusamy Babylakshmi, Kumar Pal Pramod
Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, 560029, India.
Institute of Bioinformatics, International Technology Park, Bangalore, 560066, India; Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India.
Parkinsonism Relat Disord. 2024 Dec;129:107157. doi: 10.1016/j.parkreldis.2024.107157. Epub 2024 Sep 27.
Indian Parkinson's Disease (PD) patients are severely underrepresented in terms of genetic studies and little is known about the frequency of variants and their impact on motor and nonmotor symptoms (NMS).
This retrospective cross-sectional study was conducted in PD patients undergoing treatment at a tertiary care hospital from India. Patients were advised genetic testing if they had (i) age at onset (AAO) of motor symptoms at or before 50 years (EOPD), (ii) positive family history of PD, parkinsonism or dystonia. All patients underwent whole exome sequencing and potentially pathogenic variants were identified.
Clinical and genetic data were available for 230 (163 males, 70.4 %) patients. Thirty-five pathogenic and likely pathogenic variants in various PD genes were identified in 47 patients resulting in a yield of 20.4 %. In the remaining, 82 patients had either variants of uncertain significance or had variants in genes not associated with parkinsonism and 101 patients did not have any non-benign variants. Patients with genetically mediated PD had a lower AAO and statistically greater frequency of dystonia (36.2 %), postural instability (29.8 %) and mood disorder (29.8 %) and a higher Hoehn and Yahr score (2.9). Among the 47 patients, 11 patients had PARK-PRKN, six patients had PARK-PLA2G6, and 22 patients had PARK-GBA1.
Around one-fifth of early-onset PD can have an underlying monogenetic cause. PARK-GBA1, PARK-PRKN and PARK-PLA2G6 are the commoner causes of genetically mediated PD in India. Patients with genetic cause had an earlier age at onset, and more frequent dystonia, postural instability and dyskinesia.
在基因研究方面，印度帕金森病（PD）患者的代表性严重不足，关于变异的频率及其对运动和非运动症状（NMS）的影响知之甚少。
这项回顾性横断面研究在一家来自印度的三级护理医院接受治疗的PD患者中进行。如果患者有以下情况，则建议进行基因检测：（i）运动症状的发病年龄（AAO）在50岁及以前（早发性帕金森病，EOPD），（ii）有PD、帕金森综合征或肌张力障碍的阳性家族史。所有患者均接受了全外显子测序，并鉴定了潜在的致病变异。
有230名（163名男性，占70.4%）患者的临床和基因数据可供分析。在47名患者中鉴定出各种PD基因中的35种致病和可能致病的变异，检出率为20.4%。其余患者中，82名患者有意义未明的变异或其基因变异与帕金森综合征无关，101名患者没有任何非良性变异。由基因介导的PD患者的发病年龄较低，肌张力障碍（36.2%）、姿势不稳（29.8%）和情绪障碍（29.8%）的发生率在统计学上更高，Hoehn和Yahr评分更高（2.9）。在这47名患者中，11名患者有PARK-PRKN变异，6名患者有PARK-PLA2G6变异，22名患者有PARK-GBA1变异。
约五分之一的早发性帕金森病可能有潜在的单基因病因。在印度，PARK-GBA1、PARK-PRKN和PARK-PLA2G6是基因介导的帕金森病的常见病因。有基因病因的患者发病年龄较早，肌张力障碍、姿势不稳和运动障碍更为常见。
