Molecular epidemiology of spinocerebellar ataxias in Cuba: Insights into SCA2 founder effect in Holguin
| Autor: | Raúl Aguilera Rodríguez, Dany Coello Almarales, José M. Laffita Mesa, Julio César Rodríguez Díaz, Luis Enrique Almaguer Mederos, Yanetza González Zaldívar, Roberto Rodríguez Labrada, Gilberto Sánchez Cruz, Humberto Jorge Cedeño, Nieves Santos Falcón, Karel Escalona Batallan, Luis Velázquez Pérez, Milena Paneque Herrera, Dennis Almaguer Gotay |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent Population Nerve Tissue Proteins Biology Severity of Illness Index Asymptomatic Young Adult Gene Frequency Molecular genetics Prevalence medicine Humans Spinocerebellar Ataxias Age of Onset Child education Aged Genetics education.field_of_study Molecular epidemiology Anticipation Genetic General Neuroscience Cuba Middle Aged medicine.disease Founder Effect Child Preschool Hereditary Diseases Anticipation (genetics) Spinocerebellar ataxia Female medicine.symptom Trinucleotide Repeat Expansion Founder effect |
| Zdroj: | Neuroscience Letters. 454:157-160 |
| ISSN: | 0304-3940 |
| Popis: | The objective of this study was to determine the prevalence of hereditary ataxias in Cuba, with a special focus on the clinical and molecular features of SCA2. Clinical assessments were performed by neurological examinations and application of the SARA scale. Molecular analyses of genes SCA1–3, SCA6, SCA17 and DRPLA identified 753 patients with SCA and 7173 asymptomatic relatives, belonging to 200 unrelated families. 86.79% of all SCA patients were affected with SCA2. In the Holguin province, the average population prevalence of SCA2 is 40.18 × 105 inhabitants, with the remarkable figure of 141.66 × 105 in the Baguanos municipality. The high prevalence of the SCA2 mutation in Holguin reflects most likely a founder effect. The stabilization of the prevalence along time suggests the existence of premutated chromosomes with pure CAG, acting as reservoir for further expansions. CAG repeat length correlated inversely with age at onset, accounting for 80% of the variability. Genetic anticipation was observed in the 80% of transmissions. Repeat instability was greater in paternal transmissions whereas CAG expansions without anticipation was observed in 10.97% suggesting the effect of CAA interruptions in the CAG segment, which decrease the toxicity of the abnormal ataxin-2, and/or other protective factors. |
| Databáze: | OpenAIRE |
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