Lack of full sequencing GBA1 studies for patients with Parkinson’s disease in Latin America

Santos‐Lobato, Bruno Lopes; Schumacher-Schuh, Artur; Mata, Ignacio F.

doi:10.1038/s41531-022-00358-z

Cited by 2 publications

(1 citation statement)

References 18 publications

(18 reference statements)

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“…This difference in prevalence might arise because only a third of the included studies in our systematic review fully sequenced the gene (Table S3). Similar findings have been highlighted within our region before, 112 who showed that due to gene complexity, many studies within the region performed incomplete sequencing.…”

Section: Discussionsupporting

confidence: 90%

Frequency of Hereditary and GBA1‐Related Parkinsonism in Latin America: A Systematic Review and Meta‐Analysis

Saffie Awad,

Teixeira‐dos‐Santos,

Santos‐Lobato

et al. 2023

Movement Disorders

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BackgroundIdentifying hereditary parkinsonism is valuable for diagnosis, genetic counseling, patient prioritization in trials, and studying the disease for personalized therapies. However, most studies were conducted in Europeans, and limited data exist on admixed populations like those from Latin America.ObjectivesThis study aims to assess the frequency and distribution of genetic parkinsonism in Latin America.MethodsWe conducted a systematic review and meta‐analysis of the frequency of parkinsonian syndromes associated with genetic pathogenic variants in Latin America. We defined hereditary parkinsonism as those caused by the genes outlined by the MDS Nomenclature of Genetic Movement Disorders and heterozygous carriers of GBA1 pathogenic variants. A systematic search was conducted in PubMed, Web of Science, Embase, and LILACS in August 2022. Researchers reviewed titles and abstracts, and disagreements were resolved by a third researcher. After this screening, five researchers reanalyzed the selection criteria and extracted information based on the full paper. The frequency for each parkinsonism‐related gene was determined by the presence of pathogenic/likely pathogenic variants among screened patients. Cochran's Q and I2 tests were used to quantify heterogeneity. Meta‐regression, publication bias tests, and sensitivity analysis regarding study quality were also used for LRRK2‐, PRKN‐, and GBA1‐related papers.ResultsWe included 73 studies involving 3014 screened studies from 16 countries. Among 7668 Latin American patients, pathogenic variants were found in 19 different genes. The frequency of the pathogenic variants in LRRK2 was 1.38% (95% confidence interval [CI]: 0.52–2.57), PRKN was 1.16% (95% CI: 0.08–3.05), and GBA1 was 4.17% (95% CI: 2.57–6.08). For all meta‐analysis, heterogeneity was high and publication bias tests were negative, except for PRKN, which was contradictory. Information on the number of pathogenic variants in the other genes is further presented in the text.ConclusionsThis study provides insights into hereditary and GBA1‐related parkinsonism in Latin America. Lower GBA1 frequencies compared to European/North American cohorts may result from limited access to gene sequencing. Further research is vital for regional prevalence understanding, enabling personalized care and therapies. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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Section: Discussionsupporting

confidence: 90%

Frequency of Hereditary and GBA1‐Related Parkinsonism in Latin America: A Systematic Review and Meta‐Analysis

Saffie Awad,

Teixeira‐dos‐Santos,

Santos‐Lobato

et al. 2023

Movement Disorders

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Parkinson's Disease Gene Screening in Familial Cases from Central and South America

Lorenzo‐Betancor,

Mehta,

Ramchandra

et al. 2024

Movement Disorders

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BackgroundParkinson's disease (PD) is the second most common neurodegenerative disease following Alzheimer's disease. Nearly 30 causative genes have been identified for PD and related disorders. However, most of these genes were identified in European‐derived families, and little is known about their role in Latin American populations.ObjectivesOur goal was to assess the spectrum and frequency of pathogenic variants in known PD genes in familial PD patients from Latin America.MethodsWe selected 335 PD patients with a family history of PD from the Latin American Research Consortium on the Genetics of PD. We capture‐sequenced the coding regions of 26 genes related to neurodegenerative parkinsonism. Of the 335 PD patients, 324 had sufficient sequencing coverage to be analyzed.ResultsWe identified pathogenic variants in 41 individuals (12.7%) in FBXO7, GCH1, LRRK2, PARK7, PINK1, PLA2G6, PRKN, SNCA, and TARDBP, GBA1 risk variants in 25 individuals (7.7%), and variants of uncertain significance in another 24 individuals (7.4%) in ATP13A2, ATP1A3, DNAJC13, DNAJC6, GBA1, LRKK2, PINK1, VPS13C, and VPS35. Of the 70 unique variants identified, 19 were more frequent in Latin Americans than in any other population.ConclusionsThis is the first screening of known PD genes in a large cohort of patients with familial PD from Latin America. There were substantial differences in the spectrum of variants observed in comparison to previous findings from PD families of European origin. Our data provide further evidence that differences exist between the genetic architecture of PD in Latinos and European‐derived populations. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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Lack of full sequencing GBA1 studies for patients with Parkinson’s disease in Latin America

Cited by 2 publications

References 18 publications

Frequency of Hereditary and GBA1‐Related Parkinsonism in Latin America: A Systematic Review and Meta‐Analysis

Frequency of Hereditary and GBA1‐Related Parkinsonism in Latin America: A Systematic Review and Meta‐Analysis

Parkinson's Disease Gene Screening in Familial Cases from Central and South America

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