Parkinson’s disease may be caused by a single pathogenic variant (monogenic) in 5–10% of cases, but investigation of these disorders provides valuable pathophysiological insights. In this review, we discuss each genetic form with a focus on genotype, phenotype, pathophysiology, and the geographic and ethnic distribution. Well-established Parkinson’s disease genes include autosomal dominant forms (SNCA, LRRK2, and VPS35) and autosomal recessive forms (PRKN, PINK1 and DJ1). Furthermore, mutations in the GBA gene are a key risk factor for Parkinson’s disease, and there have been major developments for X-linked dystonia parkinsonism. Moreover, atypical or complex parkinsonism may be due to mutations in genes such as ATP13A2, DCTN1, DNAJC6, FBXO7, PLA2G6, and SYNJ1. Furthermore, numerous genes have recently been implicated in Parkinson’s disease, such as CHCHD2, LRP10, TMEM230, UQCRC1, and VPS13C. Additionally, we discuss the role of heterozygous mutations in autosomal recessive genes, the effect of having mutations in two Parkinson’s disease genes, the outcome of deep brain stimulation, and the role of genetic testing. We highlight that monogenic Parkinson’s disease is influenced by ethnicity and geographical differences, reinforcing the need for global efforts to pool large numbers of patients and identify novel candidate genes.

While intron retention (IR) is now widely accepted as an important mechanism of mammalian gene expression control, it remains the least studied form of alternative splicing. To delineate conserved features of IR, we performed an exhaustive phylogenetic analysis in a highly purified and functionally defined cell type comprising neutrophilic granulocytes from five vertebrate species spanning 430 million years of evolution. Our RNA-sequencing-based analysis suggests that IR increases gene regulatory complexity, which is indicated by a strong anti-correlation between the number of genes affected by IR and the number of protein-coding genes in the genome of individual species. Our results confirm that IR affects many orthologous or functionally related genes in granulocytes. Further analysis uncovers new and unanticipated conserved characteristics of intron-retaining transcripts. We find that intron-retaining genes are transcriptionally co-regulated from bidirectional promoters. Intron-retaining genes have significantly longer 3′ UTR sequences, with a corresponding increase in microRNA binding sites, some of which include highly conserved sequence motifs. This suggests that intron-retaining genes are highly regulated post-transcriptionally. Our study provides unique insights concerning the role of IR as a robust and evolutionarily conserved mechanism of gene expression regulation. Our findings enhance our understanding of gene regulatory complexity by adding another contributor to evolutionary adaptation.

Background: Stent retriever thrombectomy has recently been found to be effective for anterior circulation strokes, but its efficacy for basilar artery occlusion (BAO) is unclear.Objective: To carry out a systematic review and meta-analysis to analyze the available evidence for the use of stent retrievers for BAO.Methods: Two independent reviewers searched six databases for studies reporting outcomes following endovascular treatment for BAO.Results: A total of 17 articles (6 prospective and 11 retrospective) were included. The weighted mean age of patients was 67 years (range 59–82) and 59% were male. Thrombolytic drugs were administered intravenously and intra-arterially in 46% (range 0–88%) and 38% (range 0–90%) of patients, respectively. Weighted pooled estimates of successful recanalization (TICI 2b–3) and good outcome (modified Rankin Scale ≤2) were 80.0% (95% CI 70.7% to 88.0%; I²=80.28%; p<0.001) and 42.8% (95% CI 34.0% to 51.8%; I²=61.83%; p=0.002), respectively. Pooled mortality was 29.4% (95% CI 23.9% to 35.3%; I²=37.01%; p=0.087). Incidence of procedure-related complications and symptomatic hemorrhage was 10.0% (95% CI 3.7% to 18.3%; I²=61.05%; p=0.017) and 6.8% (95% CI 3.5% to 10.8%; I²=37.99%; p=0.08), respectively.Conclusions: Stent retriever thrombectomy achieves a high rate of recanalization and functional independence while being relatively safe for patients with BAO. Future prospective studies with long-term follow-up are warranted.