Center for Clinical Research on Neurological Diseases, The First Affiliated Hospital, Dalian Medical University, Dalian 116021, China.
Liaoning Provincial Key Laboratory for Research on the Pathogenic Mechanisms of Neurological Diseases, The First Affiliated Hospital, Dalian Medical University, Dalian 116021, China.
Biosci Rep. 2020 May 29;40(5). doi: 10.1042/BSR20200534.
Early-onset Parkinson's disease (EOPD) is usually caused by genetic variants and patients with EOPD develop symptoms before the age of 50, accounting for 5% Parkinson's disease (PD). Here we present a Chinese Han pedigree with clinical features of EOPD. To determine the diagnosis and pathogenic mutations of this pedigree, whole exome sequencing, Sanger sequencing and real-time quantitative PCR were performed to detect all the four family members. Our results showed that a new form of compound heterozygous mutation in the PRKN gene, consisting of heterozygous point mutation c.850G > C (p.G284R) along with exon 4 deletion, is the causative genetic factor for EOPD in this pedigree. These discoveries may have implications for genetic counseling, clinical management and developing PRKN target gene therapy strategy.
早发性帕金森病（EOPD）通常由遗传变异引起，EOPD 患者在 50 岁之前出现症状，占帕金森病（PD）的 5%。本文报道了一个具有 EOPD 临床特征的中国汉族家系。为了确定该家系的诊断和致病突变，对所有 4 名家系成员进行了全外显子组测序、Sanger 测序和实时定量 PCR。结果显示，PRKN 基因的一种新的复合杂合突变形式，由杂合点突变 c.850G > C（p.G284R）和外显子 4 缺失组成，是该家系 EOPD 的致病遗传因素。这些发现可能对遗传咨询、临床管理和开发 PRKN 靶基因治疗策略具有重要意义。
