Dataset Information

Co-occurrence of ATXN3 and ATXN2 repeat expansions in Chinese ataxia patients with slow saccades.

ABSTRACT: BACKGROUND:The presence of more than one polyQ-related gene within a single individual is a rare incidence, which may provide the potential opportunity to study the combined effects of these spinocerebellar ataxia (SCA) genes. METHODS:We retrospectively analyzed genetic data from 112 SCA3 probands and found Patient 1 harbored expanded ATXN2 allele (33 repeats) and intermediate TBP allele (41 repeats), and Patient 2 with intermediate ATXN2 allele (32 repeats). Detailed clinical and oculomotor performances were investigated. The age at onset and oculomotor parameters of both patients were compared with matched pure SCA3 groups controlling either disease severity or CAG repeats. RESULTS:Most of the clinical phenotypes and oculomotor characteristics of these two patients were common to typical SCA3 patients. Compared to pure SCA3 groups controlling disease severity, mild reduced horizontal saccade velocity could be detected in both patients. However, mild expansions of the ATXN2 allele seemed to have no influence on the age at onset of Patient 1 but might have a mild impact on Patient 2. CONCLUSION:Our study provides supporting evidence that mild expansions of ATXN2 may have modifying effects on SCA3 phenotype. Larger control series and longitudinal data are warranted to confirm our results.

SUBMITTER: Wu C

PROVIDER: S-EPMC6565543 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Co-occurrence of ATXN3 and ATXN2 repeat expansions in Chinese ataxia patients with slow saccades.

Wu Chao C Cai Qiong Q You Huajing H Zhou Xiangxue X Chen Dingbang D Mo Guiling G Li Xunhua X

Molecular genetics & genomic medicine 20190328 6

<h4>Background</h4>The presence of more than one polyQ-related gene within a single individual is a rare incidence, which may provide the potential opportunity to study the combined effects of these spinocerebellar ataxia (SCA) genes.<h4>Methods</h4>We retrospectively analyzed genetic data from 112 SCA3 probands and found Patient 1 harbored expanded ATXN2 allele (33 repeats) and intermediate TBP allele (41 repeats), and Patient 2 with intermediate ATXN2 allele (32 repeats). Detailed clinical and ...[more]

PMID: 30920184

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Project description:ImportanceRepeats of CAG in the ataxin 2 gene (ATXN2) in the long-normal range (sometimes referred to as intermediate) have been identified as modifiers of amyotrophic lateral sclerosis (ALS) risk. Prior studies have used thresholding considering various cutoffs for ATXN2 repeat length.ObjectiveTo calculate association between ATXN2 CAG repeat alleles and increased risk of ALS across multiple ethnic groups.Data sourcesThe MEDLINE database was searched for studies published by December 29, 2013, reporting ATXN2 CAG repeat length in patients with ALS and controls.Study selectionStudies were included if they reported original data on relative risks or odds ratios (ORs) from ALS and control populations for individual ATXN2 alleles. Review articles that reported no new data were not included in the analysis.Data extraction and synthesisAnalysis of allele distribution was performed to ensure that all studies followed identical allele sizing. The ORs, 95% confidence intervals, and population attributable risk percentages were calculated according to standard procedures.Main outcomes and measuresOccurrence of ALS associated with ATXN2 repeat alleles, expressed as ORs.ResultsNine studies were analyzed, including 7505 controls and 6151 sporadic ALS cases. The ALS and control cohorts were recruited from different geographical and ethnic regions including the United States, French Canada/Canada, Belgium and the Netherlands, Germany, Italy, mainland China, Turkey, and Flanders-Belgium. The ATXN2 CAG repeat lengths ranged from 13 to 39 in patients with ALS and from 13 to 34 in controls. The ORs were less than 1.00 for alleles with 25 to 28 repeats. The OR was 1.55 for 30 repeats, but this elevation was not statistically significant (95% CI, 0.88-2.73). The ORs were 2.70 (95% CI, 1.47-4.93) for 31 CAG repeats, 11.09 (95% CI, 4.16-29.57) for 32 repeats, and 5.76 (95% CI, 1.79-18.57) for 33 repeats.Conclusions and relevanceIn contrast to prior studies with smaller numbers, risk for ALS associated with long-normal alleles is complex. Alleles with 27 and 28 repeats lower ALS risk slightly. The risk for ALS increases beginning with 29 repeats and reaches a maximum at 32 and 33 repeats. Of note, alleles with repeats of these lengths are known to be predisposed to meiotic expansion to full-penetrance mutant alleles. In patients with ALS, alleles with 31 to 33 repeats may have undergone preferential expansion in motor neurons during mitosis or DNA repair. Our meta-analysis provides a framework for counseling individuals with long-normal ATXN2 repeats.

Dataset Information

Co-occurrence of ATXN3 and ATXN2 repeat expansions in Chinese ataxia patients with slow saccades.

Publications

Co-occurrence of ATXN3 and ATXN2 repeat expansions in Chinese ataxia patients with slow saccades.

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