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

Abstract

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.

Analysis of SCA2 and SCA3/MJD repeats in Parkinson's disease in mainland China: Genetic, clinical, and positron emission tomography findings

“…Recent reports suggest that CAG triplet expansions of ATXN2 and MJD1 genes can cause L ‐dopa responsive Parkinsonism 1–6. In our study, we studied a large cohort of PD patients, including 386 sporadic and 66 familial cases, confirming that SCA2 and SCA3/MJD mutations may exclusively manifest as L ‐dopa‐responsive Parkinsonism.…”

“…Thus, analyses for relative gene alterations were performed to investigate the associations between PD and other neurodegenerative diseases. The results of the (CAG)n repeats expansion of ATXN2 and MJD1 gene in some PD patients described previously provided a better understanding of these associations 1–5. The high prevalence of SCA2 mutation in FPD1–5 and the report of Parkinsonism in a SCA3/MJD patient in Taiwan6 prompted us to determine the SCA2 and the SCA3/MJD frequency in PD patients in mainland China, assessing the necessity of SCA testing in Parkinsonism genetic analysis.…”

Pathophysiology of Small-Fiber Sensory System in Parkinson's Disease

“…None of the patients had clinically relevant signs of autonomic dysfunction and mutations in Parkin , PINK1 , LRRK2 , SCA2 , and SCA3 were previously excluded. 20,21 All patients were treated with L-dopa or a combination with dopamine agonists and had good clinical responses. L-dopa equivalents were calculated according to Möller et al 22 We defined the daily L-dopa dose as the average daily dosage of L-dopa in the 6 months before entering the study.…”

Mutational Analysis of Angiogenin Gene in Parkinson's Disease

“…Among PD patients, 50 had a family history of PD, 500 were sporadic late-onset PD and 200 were early-onset PD patients (onset age less than 50 years). Mutations in the a-synuclein , Parkin , PINK1 , DJ-1 , LRRK2 , ATP13A2 , HTRA2 , SCA2 , SCA3 and C9Orf72 genes were previously excluded in all familial and early-onset PD patients [10]–[15]. The diagnosis of PD was based on the UK PD Brain Bank clinical diagnostic criteria [16].…”