Neurological phenotypes in spinocerebellar ataxia type 2: Role of mitochondrial polymorphism A10398G and other risk factors

Monte, Thaís Lampert; Pereira, Fernanda Alves Cangerana; Reckziegel, Estela da Rosa; Augustin, Marina Coutinho; Locks-Coelho, Lucas D.; Santos, Amanda Senna Pereira dos; Pedroso, José Luiz; Barsottini, Orlando Graziani Póvoas; Vargas, Fernando; Saraiva-Pereira, Maria Luiza; Jardim, Laura Bannach; Neurogenética, Rede

doi:10.1016/j.parkreldis.2017.06.010

Cited by 15 publications

(12 citation statements)

References 27 publications

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“…For example, the presence of dystonia was associated with greater severity of ataxia in the spinocerebellar ataxias SCA‐ATXN1, SCA‐ATXN2, and SCA‐ATXN3 . Also, SCA‐ATXN2 and SCA‐ATXN3 patients with dystonia showed greater CAG repeat expansion . In contrast, dystonia was associated a slower progression in SCA‐CACNA1A …”

Section: Methodsmentioning

confidence: 93%

Genetic Dystonia‐ataxia Syndromes: Clinical Spectrum, Diagnostic Approach, and Treatment Options

Rossi

Balint

Vernetti

et al. 2018

Movement Disord Clin Pract

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Background Dystonia and ataxia are manifestations of numerous disorders, and indeed, an ever‐expanding spectrum of genes causing diseases that encompass dystonia and ataxia are discovered with the advances of genetic techniques. In recent years, a pathophysiological link between both clinical features and the role of the cerebellum in the genesis of dystonia, in some cases, has been proposed. In clinical practice, the genetic diagnosis of dystonia‐ataxia syndromes is a major issue for genetic counseling, prognosis and, occasionally, specific treatment. Methods For this pragmatic and educational review, we conducted a comprehensive and structured literature search in Pubmed, OMIM, and GeneReviews using the key words “dystonia” and “ataxia” to identify those genetic diseases that may combine dystonia with ataxia. Results There are a plethora of genetic diseases causing dystonia and ataxia. We propose a series of clinico‐radiological algorithms to guide their differential diagnosis depending on the age of onset, additional neurological or systemic features, and imaging findings. We suggest a sequential diagnostic approach to dystonia‐ataxia syndromes. We briefly highlight the pathophysiological links between dystonia and ataxia and conclude with a review of specific treatment implications. Conclusions The clinical approach presented in this review is intended to improve the diagnostic success of clinicians when faced with patients with dystonia‐ataxia syndromes.

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Section: Methodsmentioning

confidence: 93%

Genetic Dystonia‐ataxia Syndromes: Clinical Spectrum, Diagnostic Approach, and Treatment Options

Rossi

Balint

Vernetti

et al. 2018

Movement Disord Clin Pract

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“…Besides, the clinical subtypes of SCA2, SCA3, and dentatorubral-pallidoluysian atrophy (DRPLA) had also been reported to predict the clinical presentation and prognosis [6,13,14]. Likewise, we hypothesize that dystonia in SCAs reflects a different underlying genetic complex and suggests a different rate of ataxia progression or prognosis.…”

Section: Introductionmentioning

confidence: 76%

“…This relation had not been found before, but SCA17 patients could have dystonia [2,37–39]. In two Brazilian SCA studies, they studied on the genetic modifier candidates, including repeat expansions of ATXN1, ATXN2, ATXN3, CACNA1A, ATXN7 , and RAI1 , and they found there was no relationship between these genetic modifiers and dystonic phenotype in specific type of SCAs [6,11]. Our findings confirmed the Brazilian studies and we highlighted that interaction between repeat expansions could be an important genetic modifier for the clinical presentations of monogenetic, neurodegenerative disorders such as Huntington’s disease and SCAs [10].…”

Section: Discussionmentioning

confidence: 99%

Dystonia and ataxia progression in spinocerebellar ataxias

Kuo

Gan

Wang

et al. 2017

Parkinsonism & Related Disorders

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Background Dystonia is a common feature in spinocerebellar ataxias (SCAs). Whether the presence of dystonia is associated with different rate of ataxia progression is not known. Objectives To study clinical characteristics and ataxia progression in SCAs with and without dystonia. Methods We studied 334 participants with SCA 1, 2, 3 and 6 from the Clinical Research Consortium for Spinocerebellar Ataxias (CRC-SCA) and compared the clinical characteristics of SCAs with and without dystonia. We repeatedly measured ataxia progression by the Scale for Assessment and Rating of Ataxia every 6 months for 2 years. Regression models were employed to study the association between dystonia and ataxia progression after adjusting for age, sex and pathological CAG repeats. We used logistic regression to analyze the impact of different repeat expansion genes on dystonia in SCAs. Results Dystonia was most commonly observed in SCA3, followed by SCA2, SCA1, and SCA6. Dystonia was associated with longer CAG repeats in SCA3. The CAG repeat number in TBP normal alleles appeared to modify the presence of dystonia in SCA1. The presence of dystonia was associated with higher SARA scores in SCA1, 2, and 3. Although relatively rare in SCA6, the presence of dystonia was associated with slower progression of ataxia. Conclusions The presence of dystonia is associated with greater severity of ataxia in SCA1, 2, and 3, but predictive of a slower progression in SCA6. Complex genetic interactions among repeat expansion genes can lead to diverse clinical symptoms and progression in SCAs.

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“…Related studies reported that 10398A was associated with some systemic diseases, increasing the risk of Parkinson's disease, breast cancer, and other types (Chia‐Wei et al, ; Gui et al, ; Juo et al, ; Li et al, ; Mims et al, ; van der Walt et al, ). A recent study showed that cognitive decline was not related to any usual risk factor but to the G allele of A10398G in mtDNA (Monte et al, ), and another study suggested that the mitochondrial DNA 10398 A/G polymorphism plays a possible role in the genetic etiology of attention deficit hyperactivity disorder (ADHD) in Korean children (Hwang et al, ). Studies have found that 10398A can cause functional changes in the oxidative phosphorylation of respiratory complex I, leading to increased ROS production (Mims et al, ; Ross et al, ; van der Walt et al, ).…”

Section: Discussionmentioning

confidence: 99%

Correlation study on mtDNA polymorphisms as potential risk factors in aggressive periodontitis by NGS

2019

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Objectives Using next‐generation sequencing (NGS) to determine whether aggressive periodontitis is associated with specific mitochondrial polymorphisms. Materials and Methods A total of 165 unrelated Han Chinese were enrolled in the study. We analyzed the mitochondrial DNA (mtDNA) in 97 patients with aggressive periodontitis and 68 healthy controls by NGS. The mitochondrial DNA was L‐PCR‐amplified and subsequently sequenced by an Illumina Genome Analyzer (NGS). Chi‐square tests were used to assess the differences between the two groups. In cases of significant difference, multivariate logistic regression models were further used to analyze the association between mtDNA polymorphisms and aggressive periodontitis. Results Significant association was observed between aggressive periodontitis and eight mitochondrial polymorphisms: "8860G‐10400C" (OR = 2.828, p = .002), "8701A" (OR = 2.308, p = .005), "12705C‐10398A" (OR = 2.683, p = .002), "9540C" (OR = 3.838, p = .001) and "10873T‐15043G" (OR = 4.375, p = .001). Conclusions The pathogenesis of aggressive periodontitis is complicated, and its heredity is not well characterized. Our study was the first to use next‐generation sequencing and found that 8860G‐10400C, 8701A, 12705C‐10398A, 9540C, and 10873T‐15043G are associated with aggressive periodontitis in the Han Chinese population.

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Neurological phenotypes in spinocerebellar ataxia type 2: Role of mitochondrial polymorphism A10398G and other risk factors

Cited by 15 publications

References 27 publications

Genetic Dystonia‐ataxia Syndromes: Clinical Spectrum, Diagnostic Approach, and Treatment Options

Genetic Dystonia‐ataxia Syndromes: Clinical Spectrum, Diagnostic Approach, and Treatment Options

Dystonia and ataxia progression in spinocerebellar ataxias

Correlation study on mtDNA polymorphisms as potential risk factors in aggressive periodontitis by NGS

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