The frequency of the C9orf72 expansion in a Brazilian population

Cintra, Vívian Pedigone; Bonadia, Luciana Cardoso; Andrade, Helen Maia Tavares de; Albuquerque, Milena de; Eusébio, Mayara Ferreira; Oliveira, Daniel Sabino de; Claudino, Rinaldo; Gonçalves, Marcus Vinícius Magno; Teixeira, Antônio Lúcio; Prado, Laura de Godoy Rousseff; Souza, Leonardo Cruz de; Dourado, Mário Emílio; Oliveira, Acary Souza Bullé; Tumas, Vítor; França, Marcondes C.; Marques, Wilson

doi:10.1016/j.neurobiolaging.2018.01.007

Cited by 15 publications

(11 citation statements)

References 23 publications

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“…Indeed, a lesser proportion of Cubans with sporadic ALS carried the C9orf72 repeat expansion (2.1%) compared with the carrier rate reported in a pooled analysis of European sporadic ALS cases (5.1%) 6. In keeping with the known variations in the frequency of C9orf72 repeat expansions across different populations, the proportion of Cubans with sporadic ALS carrying the C9orf72 repeat expansion was comparable with the rate seen in other Latin-American populations (Brazil 3.6%38; Argentina 2%39) and greater than that seen in a pooled analysis of Asian sporadic ALS cases (0.3%) 6. No known SOD1 , TARDBP or FUS mutations were found in the Cuban ALS cohort studied.…”

Section: Discussionsupporting

confidence: 66%

Comparison of the clinical and genetic features of amyotrophic lateral sclerosis across Cuban, Uruguayan and Irish clinic-based populations

Ryan

Vaillant

McLaughlin

et al. 2019

J Neurol Neurosurg Psychiatry

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ObjectivesThis study compares the clinical characteristics of patients with amyotrophic lateral sclerosis (ALS) within three clinic-based populations from Cuba, Uruguay and Ireland and determines the impact of known ALS-associated genetic variants on phenotypic manifestations within the Cuban population.MethodsDemographic and clinical information was collected on 115 Cuban, 220 Uruguayan and 1038 Irish patients with ALS attending national specialist clinics through 1996–2017. All Cuban patients and 676 Irish patients underwent next-generation DNA sequencing and were screened for the pathogenic C9orf72 repeat expansion.ResultsThe mean age of onset was younger in the Cuban (53.0 years, 95% CI 50.4 to 55.6) and Uruguayan (58.2 years, 95% CI 56.5 to 60.0) populations compared with the Irish population (61.6 years, 95% CI 60.9 to 62.4). No differences in survival between populations were observed. 1.7 % (95% CI 0.6 to 4.1) of Cubans with ALS carried the C9orf72 repeat expansion compared with 9.9% (95% CI 7.8 to 12.0) of Irish patients with ALS (p=0.004). Other known variants identified in the Cuban population included ANG (one patient), CHCHD10 (one patient) and DCTN1 (three patients).Conclusions and relevanceThis study is the first to describe the clinical characteristics of ALS in Cuban and Uruguayan populations and report differences between the Cuban and Irish genetic signature in terms of known ALS-associated genetic variants. These novel clinical and genetic data add to our understanding of ALS across different and understudied populations.

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Section: Discussionsupporting

confidence: 66%

Comparison of the clinical and genetic features of amyotrophic lateral sclerosis across Cuban, Uruguayan and Irish clinic-based populations

Ryan

Vaillant

McLaughlin

et al. 2019

J Neurol Neurosurg Psychiatry

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“…The first report was in an Argentinian population, where the expansion frequency in a FTD group was similar to that reported for patients in Europe and North America ( 14 ). In a Brazilian population ( 22 , 23 ), the frequencies of the mutation in pure ALS and pure FTD cases were much lower than those observed in Finnish patients ( 11 , 24 ), but similar to what was found for Germany ( 11 ) and Flanders-Belgium ( 25 ). There are no data as yet on the frequency and heritability of this expansion in an FTD population in Colombia ( 26 ).…”

Section: Introductionsupporting

confidence: 69%

Analysis of Heritability Across the Clinical Phenotypes of Frontotemporal Dementia and the Frequency of the C9ORF72 in a Colombian Population

et al. 2021

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Frontotemporal dementia (FTD) is a highly heritable condition. Up to 40% of FTD is familial and an estimated 15% to 40% is due to single-gene mutations. It has been estimated that the G4C2 hexanucleotide repeat expansions in the C9ORF72 gene can explain up to 37.5% of the familial cases of FTD, especially in populations of Caucasian origin. The purpose of this paper is to evaluate hereditary risk across the clinical phenotypes of FTD and the frequency of the G4C2 expansion in a Colombian cohort diagnosed with FTD.Methods: A total of 132 FTD patients were diagnosed according to established criteria in the behavioral variant FTD, logopenic variant PPA, non-fluent agrammatic PPA, and semantic variant PPA. Hereditary risk across the clinical phenotypes was established in four categories that indicate the pathogenic relationship of the mutation: high, medium, low, and apparently sporadic, based on those proposed by Wood and collaborators. All subjects were also examined for C9ORF72 hexanucleotide expansion (defined as >30 repetitions).Results: There were no significant differences in the demographic characteristics of the patients between the clinical phenotypes of FTD. The higher rate phenotype was bvFTD (62.12%). In accordance with the risk classification, we found that 72 (54.4%) complied with the criteria for the sporadic cases; for the familial cases, 23 (17.4%) fulfilled the high-risk criteria, 23 (17.4%) fulfilled the low risk criteria, and 14 (10.6%) fulfilled the criteria to be classified as subject to medium risk. C9ORF72 expansion frequency was 0.76% (1/132).Conclusion: The FTD heritability presented in this research was very similar to the results reported in the literature. The C9ORF72 expansion frequency was low. Colombia is a triethnic country, with a high frequency of genetic Amerindian markers; this shows consistency with the present results of a low repetition frequency. This study provides an initial report of the frequency for the hexanucleotide repeat expansions in C9ORF72 in patients with FTD in a Colombian population and paves the way for further study of the possible genetic causes of FTD in Colombia.

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“…In 2018, a study about the frequency of this expansion in the Brazilian population was published. 23 Among the 471 patients analyzed (404 with ALS/motor neuron disease, 67 with FTD, and 63 healthy controls), the highest frequency of the expansion was in the FTD-ALS group (50% of familial and 17.6% of sporadic cases), followed by 5% of pure ALS/motor neuron disease patients (11.8% of familial and 3.6% of sporadic cases) and 7.1% of pure familial FTD individuals.…”

Section: Brazilmentioning

confidence: 94%

Genetics of dementia: insights from Latin America

Ramos

Aguillón

Cordano³

et al. 2020

Dement. neuropsychol.

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ABSTRACT. Alzheimer’s disease (AD) and frontotemporal dementia (FTD) are neurodegenerative disorders that result in a significant burden to both patients and caregivers. By 2050, the number of people with dementia in Latin America will increase 4-fold. A deep understanding of the relevant genetic factors of AD and FTD is fundamental to tackle this reality through prevention. A review of different genetic variants that cause AD or FTD in Latin America was conducted. We searched Medline and PubMed databases using the keywords “Alzheimer’s disease,” “frontotemporal dementia,” “mutation,” “America,” and “Latin America,” besides specific Latin American countries. Forty-five items were chosen and analyzed. PSEN1 mutations are the commonest cause of genetic early-onset Alzheimer’s disease (EOAD), followed by PSEN2 and APP mutations. Genetic FTD can be mainly explained by GRN and MAPT mutations, as well as C9orf72 G4C2 repeat expansion. APOE ε4 can modify the prevalence and incidence of late-onset Alzheimer’s disease (LOAD), in addition to the cognitive performance in affected carriers.

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The frequency of the C9orf72 expansion in a Brazilian population

Cited by 15 publications

References 23 publications

Comparison of the clinical and genetic features of amyotrophic lateral sclerosis across Cuban, Uruguayan and Irish clinic-based populations

Comparison of the clinical and genetic features of amyotrophic lateral sclerosis across Cuban, Uruguayan and Irish clinic-based populations

Analysis of Heritability Across the Clinical Phenotypes of Frontotemporal Dementia and the Frequency of the C9ORF72 in a Colombian Population

Genetics of dementia: insights from Latin America

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