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CC BY-NC-ND 4.0 · Arq Neuropsiquiatr 2021; 79(07): 612-623
DOI: 10.1590/0004-282X-anp-2020-0409
Article

Genetics of Parkinson’s disease in Brazil: a systematic review of monogenic forms

Genética da doença de Parkinson no Brasil: revisão sistemática de formas monogênicas
Bruno L. Santos-Lobato 
1   Universidade Federal do Pará, Laboratório de Neuropatologia Experimental, Belém PA, Brazil.
2   Hospital Ophir Loyola, Serviço de Neurologia, Belém PA, Brazil.
,
Artur Schumacher-Schuh 
3   Hospital de Clínicas de Porto Alegre, Serviço de Neurologia, Porto Alegre RS, Brazil.
4   Universidade Federal do Rio Grande do Sul, Departamento de Farmacologia, Porto Alegre RS, Brazil.
,
Ignacio F. Mata 
5   Lerner Research Institute, Genomic Medicine, Cleveland Clinic, Cleveland, OH, USA.
,
Grace H. Letro 
6   Pontifícia Universidade Católica de Campinas, Centro de Ciências da Vida, Campinas SP, Brazil.
,
Pedro Braga-Neto 
7   Universidade Federal do Ceará, Departamento de Medicina Clínica, Serviço de Neurologia e Neurocirurgia, Fortaleza CE, Brazil.
,
Pedro R. P. Brandão 
8   Universidade de Brasília, Laboratório de Neurociências e Comportamento, Brasília DF, Brazil.
,
Clécio O. Godeiro-Junior 
9   Universidade Federal do Rio Grande do Norte, Departamento de Medicina Integrada, Natal RN, Brazil.
,
Marcus V. Della Coletta 
10   Universidade do Estado do Amazonas, Fundação Hospital Adriano Jorge, Manaus AM, Brazil.
,
Sarah T. Camargos 
11   Universidade Federal de Minas Gerais, Departamento de Medicina Interna, Belo Horizonte MG, Brazil.
,
Vanderci Borges 
12   Universidade Federal de São Paulo, Departamento de Neurologia e Neurocirurgia, Setor de Transtornos de Movimento, São Paulo SP, Brazil.
,
Carlos R. M. Rieder 
13   Universidade Federal de Ciências da Saúde de Porto Alegre, Departamento de Neurologia, Porto Alegre RS, Brazil.
,
Vitor Tumas 
14   Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Neurociências e Ciências do Comportamento, Ribeirão Preto SP, Brazil.
,
on behalf of the Brazilian Consortium of Parkinson’s Disease › Institutsangaben
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ABSTRACT

Background: 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. 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. Methods: 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. Results: 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%). Conclusions: 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.

RESUMO

Introdução: Um número crescente de mutações causando formas monogênicas de doença de Parkinson (DP) tem sido descrito, principalmente entre pacientes da Europa e da América do Norte. Como a arquitetura genética varia entre diferentes populações, entender os perfis genéticos específicos de pacientes brasileiros é essencial para um melhor aconselhamento genético e para a seleção de participantes para ensaios clínicos. Objetivo: Revisão sistemática para identificar estudos genéticos brasileiros na área e definir o cenário para estudos futuros das formas monogênicas de DP no Brasil. Métodos: Nós pesquisamos as bases de dados MEDLINE, EMBASE e Web of Science desde a criação até dezembro de 2019, usando termos para “Parkinson’s disease”, “genetics” e “Brazil”. A extração de dados foi feita por dois revisores independentes. Para os genes LRRK2 e PRKN, calculamos a prevalência estimada para cada estudo e realizamos uma meta-análise. Resultados: Um total de 32 estudos foram incluídos e 94 pacientes brasileiros com DP com mutações causativas foram identificados em 2872 pacientes avaliados (3.2%). As mutações no PRKN causaram DP em 48 de 576 pacientes (8.3%). As mutações no LRRK2 foram identificadas em 40 de 1566 pacientes (2.5%), sendo a mutação mais comum a p.G2019S (2.2%). Conclusões: As mutações na PRKN são a causa mais comum de DP autossômica recessiva, e as mutações no LRRK2 a causa mais comum de DP autossômica dominante. Nós observamos uma falta de estudos epidemiológicos robustos em genética de DP, especialmente por não levar em conta a diversidade de nossa população.

Keywords:

Genetics - Parkinson’s disease - LRRK2 - PRKN

Palavras-chave:

Genética - Doença de Parkinson - LRRK2 - PRKN

Authors’ contributions:

Bruno L. Santos-Lobato, Artur Schumacher-Schuh, Ignacio F. Mata, Carlos R. M. Rieder and Vitor Tumas contributed to conception and organization of the manuscript. All authors wrote and critically evaluated the first draft of the manuscript. All authors approved the final version of the manuscript for submission.




Publikationsverlauf

Eingereicht: 25. August 2020

Angenommen: 17. September 2020

Artikel online veröffentlicht:
01. Juni 2023

© 2021. Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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