Genetics has an essential role in the development of early-onset Parkinson’s disease (EOPD). Consequently, genetic screening is of great significance for the diagnosis and treatment of EOPD. In this study, we reported two EOPD with compound heterozygous in PARKIN detected by whole-exome sequencing (WES) and ligation-dependent probe amplification (MLPA). Two unrelated EOPD patients and their parents were enrolled in this study. Genetic analysis was performed through WES and verified by direct Sanger sequencing. In addition, MLPA was used to detect exon dosage. Detailed clinical manifestations and several scale assessments were collected for genotype and phenotype analysis. Compound heterozygous mutations in PARKIN were identified in both patients. c.735−1G > A and Ex2del were detected in Case A, while G284R (c.850 G > C) and Ex2del were found in Case B. These variants were confirmed to originate from their normal parents. The c.735−1G > A is a novel PARKIN variant, which was predicted to result from disappearing of the acceptor splice site by NetGene2. The G284R is a previously reported pathological mutation and the Ex2del is a hot variant of PARKIN found in the Asian population. The phenotypes of both patients are quite different, the main manifestation of case A is rigidity onset, while the case B starts with tremor and foot dystonia. In the present study, we reported a novel compound heterozygous form of PARKIN consisting of splice variant c. 735−1G > A and Ex2del. Moreover, we also found that tiny differences in genotypes of PARKIN may lead to obvious clinical phenotypic differences.

遗传学在早发性帕金森氏病（EOPD）的发生中具有重要作用。因此，基因筛选对EOPD的诊断和治疗具有重要意义。在这项研究中，我们报道了通过全外显子组测序（WES）和连接依赖性探针扩增（MLPA）检测到的两种PARKPD中具有复合杂合性的EOPD 。两名无关的EOPD患者及其父母参加了这项研究。通过WES进行遗传分析，并通过直接Sanger测序进行验证。此外，MLPA用于检测外显子剂量。收集详细的临床表现和几种量表评估用于基因型和表型分析。PARKIN中的复合杂合突变在两名患者中均被发现。在案例A中检测到c.735-1G> A和Ex2del，而在案例B中检测到G284R（c.850 G> C）和Ex2del。这些变异被证实源自其正常父母。c.735-1G> A是一种新型的PARKIN变体，预计是NetGene2导致受体剪接位点消失的结果。该G284R是先前报道的病理突变和Ex2del是热变形PARKIN在亚洲人群中发现。两名患者的表型差异很大，病例A的主要表现是僵硬发作，而病例B则以震颤和足肌张力障碍开始。在本研究中，我们报道了一种新型的PARKIN复合杂合形式由剪接变体c。735-1G> A和Ex2del。此外，我们还发现，PARKIN基因型的微小差异可能会导致明显的临床表型差异。