In the past two decades, genetic studies of familial forms of Parkinson’s disease (PD) have shown evidence that PD has a significant genetic component. Indeed, 12 genes are strongly involved in PD causality, three of them having dominant inheritance and 9 causing early-onset autosomal recessive forms, including 3 with a typical PD and 6 with an atypical parkinsonism. The aim of this study was to determine the genetic basis of familial PD in Moroccan patients. We selected 18 Moroccan index case with familial forms of PD. Patients were first screened for exon-rearrangements by MLPA kit. They were then analyzed by gene panel next-generation sequencing (NGS). Functional variants with minor allele frequencies < 0.5% in public databases were considered potential candidate variants to PD. In the 18 PD patients with a positive family history that were analyzed, MLPA assays identified PRKN deletions in two patients: a homozygous exon 3–5 deletion and a heterozygous exon 4 deletion. Sixteen rare SNV were identified by NGS, four of them were novel. Seven mutations were categorized as pathogenic, five as likely pathogenic, two to be of uncertain significance, and 3 were predicted to be likely benign but may give a weaker pathogenic effect and could contribute to PD since they were found in late-onset PD patients. Rare or novel mutations that could be related to the disease were identified in 72% of these patients (13/18), including nine with bi-allelic pathogenic/likely pathogenic variants in genes causing recessive PD, particularly PRKN and PINK1. Mutations in genes with dominant inheritance were found in 4/18 patients (22%).

在过去的二十年中，帕金森氏病 (PD) 家族性形式的遗传研究表明，有证据表明 PD 具有重要的遗传成分。实际上，12 个基因与 PD 因果关系密切相关，其中 3 个具有显性遗传，9 个引起早发性常染色体隐性遗传，其中 3 个具有典型 PD，6 个具有非典型帕金森病。本研究的目的是确定摩洛哥患者家族性 PD 的遗传基础。我们选择了 18 个具有家族性 PD 的摩洛哥指标病例。首先通过 MLPA 试剂盒筛查患者的外显子重排。然后通过基因面板下一代测序（NGS）对它们进行分析。公共数据库中次要等位基因频率 < 0.5% 的功能变异被认为是 PD 的潜在候选变异。两名患者的PRKN缺失：纯合外显子 3-5 缺失和杂合外显子 4 缺失。NGS 鉴定出 16 种稀有 SNV，其中 4 种是新型 SNV。7 种突变被归类为致病性，5 种可能致病，2 种具有不确定的意义，3 种被预测可能是良性的，但可能会产生较弱的致病作用并可能导致 PD，因为它们是在迟发性 PD 患者中发现的。在这些患者中，72% (13/18) 发现了可能与该疾病相关的罕见或新突变，其中 9 个在导致隐性 PD 的基因中具有双等位基因致病性/可能致病性变异，特别是PRKN和PINK1。在 4/18 患者 (22%) 中发现显性遗传基因突变。