Abstract：
Parkinson\'s disease (PD) is the second most prevalent neurodegenerative disease globally, with a fast-growing prevalence. The etiology of PD exhibits a multifactorial complex nature and remains challenging. Herein, we described clinical, molecular, and integrative bioinformatics findings from a Brazilian female affected by Early-Onset PD (EOPD) harboring a recurrent homozygous pathogenic deletion in the parkin RBR E3 ubiquitin protein ligase gene (PRKN; NM_004562.3:c.155delA; p.Asn52Metfs*29; rs754809877), along with a novel heterozygous variant in the synaptojanin 1 gene (SYNJ1; NM_003895.3:c.62G > T; p.Cys21Phe; rs1486511197) found by Whole Exome Sequencing. Uncommon or unreported PRKN-related clinical features in the patient include cognitive decline, auditory and visual hallucinations, REM sleep disorder, and depression, previously observed in SYNJ1-related conditions. Moreover, PRKN interacts with endophilin A1, which is a major binding partner of SYNJ1. This protein plays a pivotal role in regulating the dynamics of synaptic vesicles, particularly in the context of endocytosis and recycling processes. Altogether, our comprehensive analyses underscore a potential synergistic effect between the PRKN and SYNJ1 variants over the pathogenesis of EOPD.
摘要：
帕金森病（PD）是全球第二大流行的神经退行性疾病，患病率快速增长。PD的病因表现出多因素复杂的性质，仍然具有挑战性。在这里，我们描述了临床，分子，和来自受早发PD（EOPD）影响的巴西女性的综合生物信息学发现，在parkinRBRE3泛素蛋白连接酶基因（PRKN;NM_004562.3：c.155delA;p.Asn52Metfs*29;rs754809877）中，以及通过全外显子组测序发现的突触素1基因中的新杂合变体（SYNJ1;NM_003895.3：c.62G>T;p.Cys21Phe;rs1486511197）。患者中不常见或未报告的PRKN相关临床特征包括认知功能减退，听觉和视觉幻觉，REM睡眠障碍,和抑郁症,先前在SYNJ1相关条件下观察到。此外，PRKN与内皮素A1相互作用，内皮素A1是SYNJ1的主要结合伴侣。这种蛋白质在调节突触小泡的动力学中起着关键作用，特别是在内吞和再循环过程中。总之,我们的综合分析强调了PRKN和SYNJ1变异体对EOPD发病机制的潜在协同作用.
