Bolivian kindred with combined spinocerebellar ataxia types 2 and 10

Baizabal‐Carvallo, José Fidel; Xia, Guangbin; Botros, P.E.; Laguna, Janeth; Ashizawa, Tetsuo; Jankovic, Joseph

doi:10.1111/ane.12371

Cited by 10 publications

(10 citation statements)

References 14 publications

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“…Thus, the rare occurrence of two distinct SCAs in the same individual, like reported by Baizabal-Carvalho et al 12 in SCA2 and SCA10 Bolivian kindred, is unlikely to have occurred in our SCA8 Brazilian family.…”

Section: Described One Patient Of Portuguesesupporting

confidence: 65%

Analysis of a fully penetrant spinocerebellar ataxia type 8 Brazilian family

et al. 2017

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Spinocerebellar ataxia type 8 (SCA8) is a progressive neurological disorder caused by the expanded repeat CTA/CTG of two overlapping genes, ATXN8OS and ATXN8, expressed bidirectionally. Normal alleles have 15-50 repeats, and pathogenic alleles range from 71 to 1300 repeats. The disorder is relatively rare, accounting for about 2%-5% of the autosomal dominant forms of hereditary ataxia worldwide. However, the prevalence of disease-causing ATXN8OS/ATXN8 expansions is higher than the disease because of the reduced penetrance of the expanded allele. The aim of this study was to describe the first fully penetrant SCA8 family showing mixed Brazilian African and Amerindian origin. Eight members of this family were evaluated-the mother and seven offspring-through a complete neurological examination conducted at the Neurogenetics Clinic, HCFMRP-USP in Brazil. The number of CTA/CTG repeats was obtained after polymerase chain reaction (PCR) and fragment analysis. The haplotype analysis was conducted using a microsatellite marker, D13S1296, and four single nucleotide polymorphisms (SNPs), rs1831189, rs8002227, rs11841483, and rs72284461, all spanning a 70.1 Mb region on chromosome 13q21.3. The molecular analysis showed that the expansions ranged from 104 to 109 CTA/CTG repeats in the six affected individuals and were absent in two asymptomatic daughters (aged 53 and 40 years). Three SNPs cosegregate with the expanded alleles, confirming the connection between expansion and disease in this family. As the SCA8 diagnosis demands careful interpretation, we suggest the use of linkage analysis to observe segregation of the mutation, making more accurate its genotyping.

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Section: Described One Patient Of Portuguesesupporting

confidence: 65%

Analysis of a fully penetrant spinocerebellar ataxia type 8 Brazilian family

et al. 2017

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“…Similarly, only 1 reference was found in the literature describing SCAs in Bolivia, a unique report of a family with 3 ataxic patients, all with SCA10 mutations, and 2 of them also presenting molecular diagnosis of SCA2. Of the SCA10 cases, 2 had epilepsy, and both affected by SCA2 had supranuclear ophthalmoplegia …”

Section: Resultsmentioning

confidence: 99%

The Geographic Diversity of Spinocerebellar Ataxias (SCAs) in the Americas: A Systematic Review

Teive

Meira

Camargo

et al. 2019

Movement Disord Clin Pract

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Background The frequency and presentation of each of the most common forms of spinocerebellar ataxias (SCAs) varies widely. In the case of the Americas, this diversity is particularly dynamic given additional social, demographic, and cultural characteristics. Objective To describe the regional prevalence and clinical phenotypes of SCAs throughout the continent. Methods A literature search was performed in both MEDLINE and LILACS databases. The research was broadened to include the screening of reference lists of systematic review articles for additional studies. Investigations dating from the earliest available through 2019. Only studies in English, Portuguese, and Spanish were included. We analyzed publications with genetically confirmed cases only, ranging from robust samples with epidemiological data to case reports and case series from each country or regions. Results Overall, SCA3 is the most common form in the continent. Region‐specific prevalence and ranking of the common forms vary. On the other hand, region‐specific phenotypic variations were not consistently found based on the available literature analyzed, with the exception of the absence of epilepsy in SCA10 consistently described in a particular cluster of cases in South Brazil. Conclusion Systematic, multinational studies analyzing in detail the true frequencies of SCAs across the Americas as well as distinct clinical signs and clues of each form would be ideal to look for these potential variations.

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“…SCA10 cases have been primarily found in Latin American countries including Mexico, 6 Brazil, 12 Colombia, 14 Argentina, 15 Peru, 16 Bolivia, 17 and Venezuela, 18 but single cases or families of SCA10 have also been reported in the USA 13 and China. 19 The prevalence of SCA10 among autosomal-dominant spinocerebellar syndromes has been reported highest in Mexico (13.9% reported cases) 6 and ranges between 3 and 11.8% in Brazil 5 , 12 , 20 and 4.7% in Venezuela.…”

Section: Introductionmentioning

confidence: 99%

Parkinson’s disease associated with pure ATXN10 repeat expansion

Schüle

McFarland

Lee

et al. 2017

npj Parkinson's Disease

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Large, non-coding pentanucleotide repeat expansions of ATTCT in intron 9 of the ATXN10 gene typically cause progressive spinocerebellar ataxia with or without seizures and present neuropathologically with Purkinje cell loss resulting in symmetrical cerebellar atrophy. These ATXN10 repeat expansions can be interrupted by sequence motifs which have been attributed to seizures and are likely to act as genetic modifiers. We identified a Mexican kindred with multiple affected family members with ATXN10 expansions. Four affected family members showed clinical features of spinocerebellar ataxia type 10 (SCA10). However, one affected individual presented with early-onset levodopa-responsive parkinsonism, and one family member carried a large repeat ATXN10 expansion, but was clinically unaffected. To characterize the ATXN10 repeat, we used a novel technology of single-molecule real-time (SMRT) sequencing and CRISPR/Cas9-based capture. We sequenced the entire span of ~5.3–7.0 kb repeat expansions. The Parkinson’s patient carried an ATXN10 expansion with no repeat interruption motifs as well as an unaffected sister. In the siblings with typical SCA10, we found a repeat pattern of ATTCC repeat motifs that have not been associated with seizures previously. Our data suggest that the absence of repeat interruptions is likely a genetic modifier for the clinical presentation of l-Dopa responsive parkinsonism, whereas repeat interruption motifs contribute clinically to epilepsy. Repeat interruptions are important genetic modifiers of the clinical phenotype in SCA10. Advanced sequencing techniques now allow to better characterize the underlying genetic architecture for determining accurate phenotype–genotype correlations.

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Bolivian kindred with combined spinocerebellar ataxia types 2 and 10

Cited by 10 publications

References 14 publications

Analysis of a fully penetrant spinocerebellar ataxia type 8 Brazilian family

Analysis of a fully penetrant spinocerebellar ataxia type 8 Brazilian family

The Geographic Diversity of Spinocerebellar Ataxias (SCAs) in the Americas: A Systematic Review

Parkinson’s disease associated with pure ATXN10 repeat expansion

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