Frequencies of spinocerebellar ataxia subtypes in Thailand: window to the population history?

Sura, Thanyachai; Eu-ahsunthornwattana, Jakris; Youngcharoen, Supak; Busabaratana, Manisa; Dejsuphong, Donniphat; Trachoo, Objoon; Theerasasawat, Supischa; Tunteeratum, Atchara; Noparutchanodom, Chinnakrit; Tunlayadechanont, Supoch

doi:10.1038/jhg.2009.27

Cited by 11 publications

(9 citation statements)

References 30 publications

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“…The frequency of MJD in the 138 SCA families involved in our study was 72.5%, which is, as far as we know, the highest rate in Asia based on studies of the Chinese mainland individuals [22-25], Chinese Taiwanese [26,27], Singaporean [28], Japanese [9,29-35], Thais[36] Korean [37,38] and Indian [10,12,39-43]. Moreover, it is one of the highest worldwide, with only Portuguese and Brazilian populations exhibiting higher proportions [11,13,16,17,44-56].…”

Section: Discussionmentioning

confidence: 69%

High frequency of Machado-Joseph disease identified in Southeastern Chinese kindreds with spinocerebellar ataxia

Gan

Shi

et al. 2010

BMC Med Genet

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BackgroundMachado-Joseph disease (MJD), caused by a CAG repeat expansion located in exon10 of the ATXN3 gene, is now regarded as one of the most common spinocerebellar ataxia (SCA) in the world. The relative frequency of MJD among SCA has previously been estimated at about 50% in the Chinese population and has been reported to be related to the frequency of large normal alleles in some populations. Taq polymerase has been used for PCR in nearly all studies reported previously.MethodsNormal and expanded alleles of ATXN3 were detected via PCR using LA Taq DNA polymerase (better for GC-rich sequences) and denaturing polyacrylamide gel electrophoresis in 150 normal individuals and 138 unrelated probands from autosomal dominant SCA families. To compare reaction efficiency, 12 MJD patients' expanded alleles were amplified with La Taq and Taq polymerase respectively in the same amplifying systems and reaction conditions.ResultsNormal alleles ranged from 12 to 42 CAG repeats. The most common allele contained 14 repeats with a frequency of 23.3%, which corroborates previous reports. The frequency of large normal alleles (>27 repeats) was 0.28, which was very high relative to previous reports. The frequency of MJD in SCA patients was 72.5%, which was significantly higher than those in previous reports about the Chinese and other Asian populations. This frequency was one of the highest reported worldwide, with only Portuguese and Brazilian populations exhibiting higher proportions. All 12 expanded alleles were amplified in PCR with La Taq polymerase, whereas only 2 expanded alleles were amplified with Taq polymerase.ConclusionWe have first reported the highest relative frequency of MJD in Asia, and we attribute this high frequency to a more efficient PCR using LA Taq polymerase and hypothesized that large ANs may act as a reservoir for expanded alleles in the Southeastern Chinese population.

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Section: Discussionmentioning

confidence: 69%

High frequency of Machado-Joseph disease identified in Southeastern Chinese kindreds with spinocerebellar ataxia

Gan

Shi

et al. 2010

BMC Med Genet

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“…MJD is the most common SCA in the Thai population followed by SCA1, SCA2 and SCA6 [24]. Over the past 15 years, the study group has had experience of seeing over a hundred Thai SCA families.…”

Section: Introductionmentioning

confidence: 99%

Clinical analysis of adult-onset spinocerebellar ataxias in Thailand

et al. 2014

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BackgroundNon-ataxic symptoms of spinocerebellar ataxias (SCAs) vary widely and often overlap with various types of SCAs. Duration and severity of the disease and genetic background may play a role in such phenotypic diversity. We conducted the study in order to study clinical characteristics of common SCAs in Thailand and the factors that may influence their phenotypes.Methods131 (49.43%) out of 265 Thai ataxia families with cerebellar degeneration had positive tests for SCA1, SCA2, Machado-Joseph disease (MJD) or SCA6. The study evaluated 83 available families including SCA1 (21 patients), SCA2 (15), MJD (39) and SCA6 (8). Comparisons of frequency of each non-ataxic sign among different SCA subtypes were analysed. Multivariate logistic regression analyses were undertaken to analyze parameters in association with disease severity and size of CAG repeat.ResultsMean ages at onset were not different among patients with different SCAs (40.31 ± 11.33 years, mean ± SD). Surprisingly, SCA6 patients often had age at onset and phenotypes indistinguishable from SCA1, SCA2 and MJD. Frequencies of ophthalmoparesis, nystagmus, hyperreflexia and areflexia were significantly different among the common SCAs, whilst frequency of slow saccade was not. In contrast to Caucasian patients, parkinsonism, dystonia, dementia, and facial fasciculation were uncommon in Thai patients. Multivariate logistic regression analysis demonstrated that ophthalmoparesis (p < 0.001) and sensory impairment (p = 0.025) were associated with the severity of the disease.ConclusionsWe described clinical characteristics of the 4 most common SCAs in Thailand accounting for almost 90% of familial spinocerebellar ataxias. There were some different observations compared to Caucasian patients including earlier age at onset of SCA6 and the paucity of extrapyramidal features, cognitive impairment and facial fasciculation. Severity of the disease, size of the pathological CAG repeat allele, genetic background and somatic heterogeneity of pathological alleles may influence clinical expressions of these common SCAs.

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“…Many studies examine the prevalence of genetically identifiable ataxias based on highly selected referral populations or referral laboratories. Such data have been summarized for the autosomal dominant ataxias (spinocerebellar ataxias or SCAs) by Schols et al and additional studies have been done in different countries . Worldwide, the most common SCA is SCA 3 (21%), followed by SCA 6 and SCA 2 (15% each), but these figures vary widely from region to region often due to founder effects.…”

Section: Epidemiological Issuesmentioning

confidence: 99%

Degenerative Ataxias: challenges in clinical research

Subramony

2016

Ann Clin Transl Neurol

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The degenerative ataxias are a very heterogeneous group of disorders that include numerous genetic diseases as well as apparently “sporadic” entities. There has been an explosion of discoveries related to genetic defects and related pathomechanisms that has brought us to the threshold of meaningful therapies in some but not all of these diseases. There also continues to be lack of knowledge of the causation of disease in a sizeable proportion of these patients. The overall rarity of ataxias as a whole and certainly of the individual genetic entities together with slow and variable progression and variable prognosis in juxtaposition with a rapid development of possible therapies in the horizon such as gene replacement and gene knock‐down strategies places the ataxias in a unique position distinct from other similar neurodegenerative diseases. The pace of laboratory research seems not matched by the pace of clinical research and clinical trial readiness. This review summarizes the author's views on the various challenges in translational research in ataxias and hopes to stimulate further thought and discussions on how to bring real help to these patients.

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Frequencies of spinocerebellar ataxia subtypes in Thailand: window to the population history?

Cited by 11 publications

References 30 publications

High frequency of Machado-Joseph disease identified in Southeastern Chinese kindreds with spinocerebellar ataxia

High frequency of Machado-Joseph disease identified in Southeastern Chinese kindreds with spinocerebellar ataxia

Clinical analysis of adult-onset spinocerebellar ataxias in Thailand

Degenerative Ataxias: challenges in clinical research

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