Abstract
Increasing numbers of mutations causing monogenic forms of Parkinson's disease (PD) have been described, mostly among patients in Europe and North America. Since genetic architecture varies between different populations, studying the specific genetic profile of Brazilian patients is essential for improving genetic counseling and for selecting patients for clinical trials. We conducted a systematic review to identify genetic studies on Brazilian patients and to set a background for future studies on monogenic forms of PD in Brazil. We searched MEDLINE, EMBASE and Web of Science from inception to December 2019 using terms for "Parkinson's disease", "genetics" and "Brazil". Two independent reviewers extracted the data. For the genes LRRK2 and PRKN, the estimated prevalence was calculated for each study, and a meta-analysis was performed. A total of 32 studies were included, comprising 94 Brazilian patients with PD with a causative mutation, identified from among 2,872 screened patients (3.2%). PRKN mutations were causative of PD in 48 patients out of 576 (8.3%). LRRK2 mutations were identified in 40 out of 1,556 patients (2.5%), and p.G2019S was the most common mutation (2.2%). PRKN is the most common autosomal recessive cause of PD, and LRRK2 is the most common autosomal dominant form. We observed that there was a lack of robust epidemiological studies on PD genetics in Brazil and, especially, that the diversity of Brazil's population had not been considered.
Highlights
IntroductionMutations in several genes have been linked to inherited forms of Parkinson’s disease (PD)
Over recent decades, mutations in several genes have been linked to inherited forms of Parkinson’s disease (PD)
After alpha-synuclein gene (SNCA) mutations were reported to be a monogenic cause of parkinsonism1, several other genetic forms of the disease were described, including those with autosomal dominant inheritance, such as with the genes LRRK2, SNCA, VPS35, ATXN2 and GCH1, and others with recessive inheritance, such as with the genes PRKN, PINK1 and DJ1
Summary
Mutations in several genes have been linked to inherited forms of Parkinson’s disease (PD). After alpha-synuclein gene (SNCA) mutations were reported to be a monogenic cause of parkinsonism, several other genetic forms of the disease were described, including those with autosomal dominant inheritance, such as with the genes LRRK2, SNCA, VPS35, ATXN2 and GCH1, and others with recessive inheritance, such as with the genes PRKN, PINK1 and DJ1. Mutations in the X-linked RAB39B gene have been described as causing parkinsonism1 Some of these mutations, such as the LRRK2 point mutation c.6055G>A (p.G2019S), are highly population-specific. Increasing numbers of mutations causing monogenic forms of Parkinson’s disease (PD) have been described, mostly among patients in Europe and North America. Objective: We conducted a systematic review to identify genetic studies on Brazilian patients and to set a background for future studies on monogenic forms of PD in Brazil. We observed that there was a lack of robust epidemiological studies on PD genetics in Brazil and, especially, that the diversity of Brazil’s population had not been considered
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