Prevalence of GBA p.K198E mutation in Colombian and Hispanic populations

Tipton, Philip W.; Soto-Beasley, Alexandra I.; Walton, Ronald L.; Soler-Rangel, Silvia; Romero-Osorio, Óscar; Díaz, Cindy; Ross, Owen A.; Wszołek, Zbigniew K.; Cerquera-Cleves, Catalina

doi:10.1016/j.parkreldis.2020.03.008

Cited by 7 publications

(5 citation statements)

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“…Most of the , most of our patients were graded in the "2.5" and "3" categories of the H&Y scale with a median for S&E score of 80% (80-90%). The median value for the MoCA test was 22 (17)(18)(19)(20)(21)(22)(23)(24)(25). There were no statistically significant differences between sex, regarding these scores.…”

Section: Sociodemographic and Clinical Variablesmentioning

confidence: 80%

“…GBA mutations have also been studied in few Latin American cohorts but mainly focused on most frequently reported mutations in other populations. The observed frequency of these mutations varies across regions ranging from 0.2% (p.N370S) to 0.7% (p.E326K) in Ecuadorians (23) and up to 5.5% (p.L444P) in Mexican Mestizo and Brazilian cohorts (23)(24)(25)(26)(27). Few studies have studied the entire GBA gene in Latin America, showing a frequency similar to those reported in individuals of European descent (4-5%), but lower than frequencies reported in Ashkenazi patients (20%) (28).…”

Section: Introductionmentioning

confidence: 99%

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Clinical and Genetic Analysis of Costa Rican Patients With Parkinson's Disease

Torrealba‐Acosta

Prada

et al. 2021

Front. Neurol.

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Background: Most research in genomics of Parkinson's disease (PD) has been done in subjects of European ancestry, leading to sampling bias and leaving Latin American populations underrepresented. We sought to clinically characterize PD patients of Costa Rican origin and to sequence familial PD and atypical parkinsonism-associated genes in cases and controls.Methods: We enrolled 118 PD patients with 97 unrelated controls. Collected information included demographics, exposure to risk and protective factors, and motor and cognitive assessments. We sequenced coding and untranslated regions in familial PD and atypical parkinsonism-associated genes including GBA, SNCA, VPS35, LRRK2, GCH1, PRKN, PINK1, DJ-1, VPS13C, and ATP13A2.Results: Mean age of PD probands was 62.12 ± 13.51 years; 57.6% were male. The frequency of risk and protective factors averaged ~45%. Physical activity significantly correlated with better motor performance despite years of disease. Increased years of education were significantly associated with better cognitive function, whereas hallucinations, falls, mood disorders, and coffee consumption correlated with worse cognitive performance. We did not identify an association between tested genes and PD or any damaging homozygous or compound heterozygous variants. Rare variants in LRRK2 were nominally associated with PD; six were located between amino acids p.1620 and 1623 in the C-terminal-of-ROC (COR) domain of Lrrk2. Non-synonymous GBA variants (p.T369M, p.N370S, and p.L444P) were identified in three healthy individuals. One PD patient carried a pathogenic GCH1 variant, p.K224R.Discussion: This is the first study that describes sociodemographics, risk factors, clinical presentation, and genetics of Costa Rican patients with PD, adding information to genomics research in a Latino population.

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Section: Sociodemographic and Clinical Variablesmentioning

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Clinical and Genetic Analysis of Costa Rican Patients With Parkinson's Disease

Torrealba‐Acosta

Prada

et al. 2021

Front. Neurol.

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“…This review assessed 3014 studies, of which 73 met the inclusion criteria 20,35–106 . The process detailing the step‐by‐step inclusion and exclusion criteria is summarized in the PRISMA flow diagram 107 shown in Figure S2.…”

Section: Resultsmentioning

confidence: 99%

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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“…Furthermore, studies have identified specific variants unique to certain populations, such as GBA1 p.K237E reported in some Latin American cohorts, which have not been found in other groups and whose phenotype is not yet widely described. 118,119 In the broader context, individuals carrying the most frequently described GBA1 mutations often show a phenotype characterized by more rapid disease progression, impaired visual cognitive tasks and olfaction, increased psychosis, and a higher likelihood of developing dementia compared with non-carriers. 120,121 The estimated disease penetrance in heterozygous carriers is low, ranging from 8% to 30% in studies performed on individuals of European and Ashkenazi Jewish ancestry.…”

Section: Parkinson's Disease Heterogeneity On the Phenotypic And Geno...mentioning

confidence: 99%

“…Although the rs3115534‐G does not appear to be linked with GD, 7 larger cohort studies are needed to uncover the phenotypic relationship of this locus in this population and its impact on glucocerebrosidase activity and PD pathogenesis. Furthermore, studies have identified specific variants unique to certain populations, such as GBA1 p.K237E reported in some Latin American cohorts, which have not been found in other groups and whose phenotype is not yet widely described 118,119 . In the broader context, individuals carrying the most frequently described GBA1 mutations often show a phenotype characterized by more rapid disease progression, impaired visual cognitive tasks and olfaction, increased psychosis, and a higher likelihood of developing dementia compared with non‐carriers 120,121 …”

Section: Introductionmentioning

confidence: 99%

Towards a Global View of Parkinson's Disease Genetics

Khani,

Cerquera‐Cleves,

Kekenadze

et al. 2024

Annals of Neurology

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Parkinson's disease (PD) is a global health challenge, yet historically studies of PD have taken place predominantly in European populations. Recent genetics research conducted in non‐European populations has revealed novel population‐specific genetic loci linked to PD risk, highlighting the importance of studying PD globally. These insights have broadened our understanding of PD etiology, which is crucial for developing disease‐modifying interventions. This review comprehensively explores the global genetic landscape of PD, emphasizing the scientific rationale for studying underrepresented populations. It underscores challenges, such as genotype–phenotype heterogeneity and inclusion difficulties for non‐European participants, emphasizing the ongoing need for diverse and inclusive research in PD. ANN NEUROL 2024

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Prevalence of GBA p.K198E mutation in Colombian and Hispanic populations

Cited by 7 publications

References 5 publications

Clinical and Genetic Analysis of Costa Rican Patients With Parkinson's Disease

Clinical and Genetic Analysis of Costa Rican Patients With Parkinson's Disease

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

Towards a Global View of Parkinson's Disease Genetics

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