Genetic characterization of Spinocerebellar ataxia 1 in a South Indian cohort
| Autor: | Gaiti Hasan, Mathew Alexander, Jayaprakash Muliyil, Reginald George Alex Tharmaraj, Dhanya Kumaran, Ajith Sivadasan, Kuryan George, Krishnan Balagopal, Sanjith Aaron, Sumita Danda |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Male Spinocerebellar Ataxia Type 1 Genotype Population India Nerve Tissue Proteins Biology Polymorphism Single Nucleotide White People Cohort Studies Young Adult Autosomal dominant cerebellar ataxia Spinocerebellar ataxia 1 Genetics medicine Humans Spinocerebellar Ataxias Genetics(clinical) Age of Onset Allele Founder mutation education Ataxin-1 Genetics (clinical) education.field_of_study Cohort Nuclear Proteins Middle Aged medicine.disease Founder Effect Pedigree Ataxins Pre-symptomatic Spinocerebellar ataxia Female Age of onset Trinucleotide Repeat Expansion Trinucleotide repeat expansion Research Article Founder effect |
| Zdroj: | BMC Medical Genetics |
| ISSN: | 1471-2350 |
| DOI: | 10.1186/s12881-014-0114-5 |
| Popis: | Background Spinocerebellar ataxia type 1 (SCA1) is a late onset autosomal dominant cerebellar ataxia, caused by CAG triplet repeat expansion in the ATXN1 gene. The frequency of SCA1 occurrence is more in Southern India than in other regions as observed from hospital-based studies. However there are no reports on variability of CAG repeat expansion, phenotype-genotype association and founder mutations in a homogenous population from India. Methods Genomic DNA isolated from buccal mouthwash of the individuals in the cohort was used for PCR-based diagnosis of SCA1. Subsequently SNP’s found within the ATXN1 loci were identified by Taqman allelic discrimination assays. Significance testing of the genotype-phenotype associations was calculated by Kruskal-Wallis ANOVA test with post-hoc Dunnett’s test and Pearson’s correlation coefficient. Results By genetic analysis of an affected population in Southern India we identified 21 pre-symptomatic individuals including four that were well past the average age of disease onset of 44 years, 16 symptomatic and 63 normal individuals. All pre-symptomatic cases harbor “pure” expansions of greater than 40 CAGs. Genotyping to test for the presence of two previously identified SNPs showed a founder effect of the same repeat carrying allele as in the general Indian population. We show that SCA1 disease onset is significantly delayed when transmission of the disease is maternal. Conclusions Our finding of early disease onset in individuals with a paternally inherited allele could serve as valuable information for clinicians towards early detection of SCA1 in patients with affected fathers. Identification of older pre-symptomatic individuals (n = 4) in our cohort among individuals with a shared genetic and environmental background, suggests that second site genetic or epigenetic modifiers might significantly affect SCA1 disease progression. Moreover, such undetected SCA1 cases could underscore the true prevalence of SCA1 in India. |
| Databáze: | OpenAIRE |
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