Department of Obstetrics and Gynecology, Faculty of Medicine, University of Granada, 18016 Granada, Spain.
Pediatric Neurology Department, Hospital Virgen de las Nieves, 18014 Granada, Spain.
Int J Mol Sci. 2024 Sep 9;25(17):9754. doi: 10.3390/ijms25179754.
This study aimed to elucidate the genetic causes underlying the juvenile parkinsonism (JP) diagnosed in a girl with several family members diagnosed with spinocerebellar ataxia type 2 (SCA2). To achieve this, whole-exome sequencing, analysis of CAG repeats, RNA sequencing analysis on fibroblasts, and metabolite identification were performed. As a result, a homozygous missense mutation SNP T>C (rs2254562) in synaptojamin 1 (SYNJ1), which has been implicated in the regulation of membrane trafficking in the synaptic vesicles, was identified. Additionally, we observed overexpression of L1 cell adhesion molecule (L1CAM), Cdc37, GPX1, and GPX4 and lower expression of ceruloplasmin in the patient compared to the control. We also found changes in sphingolipid, inositol, and inositol phosphate metabolism. These findings help to clarify the mechanisms of JP and suggest that the etiology of JP in the patient may be multifactorial. This is the first report of the rs2254562 mutation in the SYNJ gene identified in a JP patient with seizures and cognitive impairment.
本研究旨在阐明一名患有少年帕金森病（JP）的女孩的遗传病因，该女孩的几个家庭成员被诊断患有脊髓小脑共济失调 2 型（SCA2）。为此，进行了全外显子组测序、CAG 重复分析、成纤维细胞 RNA 测序分析和代谢物鉴定。结果发现，突触结合蛋白 1（SYNJ1）中的纯合错义突变 SNP T>C（rs2254562），该突变已被证实与突触小泡中膜转运的调节有关。此外，与对照组相比，我们观察到患者中 L1 细胞黏附分子（L1CAM）、Cdc37、GPX1 和 GPX4 的过度表达以及铜蓝蛋白的表达降低。我们还发现鞘脂、肌醇和肌醇磷酸盐代谢的变化。这些发现有助于阐明 JP 的发病机制，并提示该患者 JP 的病因可能是多因素的。这是首例报道在伴有癫痫和认知障碍的 JP 患者中发现 SYNJ 基因中的 rs2254562 突变。
