Presence of spinocerebellar ataxia type 2 gene mutation in a patient with apparently sporadic Parkinson's disease: Clinical implications

Shan, Din E.; Liu, Ru‐Shi; Sun, Chen; Lee, Shwn Jen; Liao, Kwong Kum; Soong, Bing Wen

doi:10.1002/mds.20212

Cited by 33 publications

(28 citation statements)

References 18 publications

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“…However, a close follow-up of these cases to see any development of cerebellar dysfunction or atypical features in the future, and further study in a large scale of SCA3 genetic screening in PD are needed to clarify the contribution of borderline expansion of SCA3 gene in the causes of PD. Since the first report of SCA2 gene mutation found in a large Chinese family with parkinsonism [Gwinn-Hardy et al, 2000], a serious of subsequent studies demonstrated that the mutation frequency of SCA2 in familial PD is around 10% [Shan et al, 2001;Lu, 2004a] and 0.4% for sporadic PD [Shan, 2004] in Taiwanese ethnic Chinese (Table II). In Singapore, SCA2 mutation rate in Chinese population is about 2.2% in early-onset sporadic PD [Lim et al, 2006].…”

Section: Discussionmentioning

confidence: 97%

Lack of mutations in spinocerebellar ataxia type 2 and 3 genes in a Taiwanese (ethnic Chinese) cohort of familial and early‐onset parkinsonism

Lin

Hwu

Chiang

et al. 2007

American J of Med Genetics Pt B

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Recent reports suggest that CAG triplet expansions of spinocerebellar ataxia type 2 and 3 (SCA2 and SCA3) genes are the cause of typical levodopa-responsive Parkinson's disease (PD) in familial cases, several of which were ethnic Chinese. To investigate the role of SCA2 and SCA3 mutations in Chinese familial and early-onset PD patients, we analyzed CAG triplet repeat expansions of SCA2 and SCA3 genes in a cohort of 73 Taiwanese/Ethnic Chinese familial and early-onset PD patients [mean age at onset 42.70 +/- 7.17 years (mean +/- SD)]. Thirteen of them (17.8%) had positive family history. All patients received comprehensive clinical evaluation including a thorough neurological examination, laboratory tests, and neuroimaging studies to exclude secondary causes and atypical parkinsonism. The CAG repeat length in these genes was determined using polymerase chain reaction polyacrylamide gel electrophoresis. SCA2 gene CAG repeats ranged from 15 to 26 repeats with a median of 20, and SCA3 gene CAG repeats ranged from 15 to 40 with a median of 15. No long pathogenic repeats were found in either SCA2 or SCA3, although borderline CAG repeat number was detected in the SCA3 gene of four patients. Thus, mutations of SCA2 or SCA3 did not play a major role in familial or early-onset PD in our study cohort. PD patients without autosomal dominant family history or obvious cerebellar ataxia should not be candidates for routine screening of SCA2 or SCA3 mutations for cost-effectiveness.

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Section: Discussionmentioning

confidence: 97%

Lack of mutations in spinocerebellar ataxia type 2 and 3 genes in a Taiwanese (ethnic Chinese) cohort of familial and early‐onset parkinsonism

Lin

Hwu

Chiang

et al. 2007

American J of Med Genetics Pt B

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“…However, few presented parkinsonism without ataxia, even after 30 years of follow‐up . Many parkinsonian patients descriptions resembled those of idiopathic PD (iPD) patients, sharing clinical features, such as asymmetric onset, late age at onset, slow progression, and good response to DRT . However, one third of patients with isolated parkinsonism exhibited cerebellar or brainstem atrophy on MRI.…”

Section: Discussionmentioning

confidence: 99%

Movement Disorders in Autosomal Dominant Cerebellar Ataxias: A Systematic Review

Rossi

Pérez-Lloret

Cerquetti

et al. 2014

Movement Disord Clin Pract

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Autosomal dominant cerebellar ataxias (ADCAs) are clinically heterogeneous disorders classified according to genetic subtype and collectively known as SCAs. In a few SCAs, movement disorders can be the most frequent extracerebellar sign. The aim of this article is to perform a systematic review of movement disorders frequency and characteristics in ADCAs. This work consisted of a structured search of electronic databases up to January 2013. Publications containing descriptions of ADCA clinical features written in several languages were selected initially based on title and abstract screening, followed by full-text reading of potentially relevant publications. Clinical findings and demographic data on genetically confirmed patients were extracted. Analysis of individual patient data from subjects with movement disorders was performed using the chi-square test and logistic regression. One thousand and sixty-six publications reviewing 12,151 patients from 30 different SCAs were analyzed. Individual data were available from 755 patients with at least one type of movement disorder during overall disease course. Of 422 patients in whom onset symptom data were available, one third referred a movement disorder as the initial symptom. During overall disease course, parkinsonism was common in many SCA subtypes, frequently described in the absence of ataxia and characterized as responding to dopaminergic medications. Motor complications developed occasionally in some patients as did nigrostriatal imaging alterations. Other frequent features were dystonia, chorea, and myoclonus. Rare conditions, such as akathisia, paroxysmal nonkinesigenic dyskinesia, or stiff person-like syndrome, were also reported. ADCA descriptions included a full range of movement disorders. Aside from postural or intention tremor, dopamine-responsive parkinsonism and dystonia were the most common.

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“…ATXN-2 alleles ranging from 32 to 43 repeats with at least one CAA interruption have been reported in SCA2 patients with parkinsonism, in familial Parkinson and in sporadic Parkinson ( Hussey et al 2002;Payami et al 2003;Furtado et al 2004;Lu et al 2004;Shan et al 2004;Kim et al 2007;Charles et al 2007;Silveira et al 2002). Conversely, classical spinocerebellar ataxia type 2 patients always carry expanded alleles with uninterrupted CAG repeats.…”

Section: Discussionmentioning

confidence: 99%

ATXN-2 CAG repeat expansions are interrupted in ALS patients

Corrado

Mazzini²,

Oggioni³

et al. 2011

Hum Genet

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It has recently been suggested that short expansions of CAG repeat in the gene ATXN-2 causing SCA2 (spinocerebellar ataxia type 2) are associated with an increased risk of amyotrophic lateral sclerosis (ALS) in the populations of the USA and northern Europe. In this study, we investigated the role of ATXN-2 in Italian patients clinically diagnosed with ALS and characterized the molecular structure of ATXN-2 expansions. We assessed the size of the CAG repeat in ATXN-2 exon 1 in 232 Italian ALS patients and 395 matched controls. ATXN-2 expanded alleles containing > 30 repeats have been observed in seven sporadic ALS patients (3.0%), while being absent in the controls (p = 0.00089). Four out of the seven patients had an ATXN-2 allele in the intermediate-fully pathological range: one with 32 repeats, 2 with 33 repeats and 1 with 37 repeats, accounting for 1.7% of the ALS cohort. Sequencing of expanded (> 32) alleles showed that they were all interrupted with at least one CAA triplet. ATXN-2 alleles with the same length and structure have been reported in SCA2 patients with parkinsonism or in familial and sporadic Parkinson. Conversely, the phenotype of the present patients was typically ALS with no signs or symptoms of ataxia or parkinsonism. In conclusion, the findings of ATXN-2 expansions in pure ALS cases suggest that ALS may be a third phenotype (alongside ataxia/parkinsonism and pure Parkinson) associated with ATXN-2 interrupted alleles.

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Presence of spinocerebellar ataxia type 2 gene mutation in a patient with apparently sporadic Parkinson's disease: Clinical implications

Cited by 33 publications

References 18 publications

Lack of mutations in spinocerebellar ataxia type 2 and 3 genes in a Taiwanese (ethnic Chinese) cohort of familial and early‐onset parkinsonism

Lack of mutations in spinocerebellar ataxia type 2 and 3 genes in a Taiwanese (ethnic Chinese) cohort of familial and early‐onset parkinsonism

Movement Disorders in Autosomal Dominant Cerebellar Ataxias: A Systematic Review

ATXN-2 CAG repeat expansions are interrupted in ALS patients

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