Yao Zhou1, Yanchun Yuan1, Zhen Liu1, Sheng Zeng1, Zhao Chen1, Lu Shen1,2,3,4, Hong Jiang1,2,3,4, Kun Xia2, Beisha Tang1,2,3,4, Junling Wang5,6,7,8. 1. Department of Neurology, Xiangya Hospital, Central South University, 87 Xiangya Rd, Changsha, Hunan, People's Republic of China. 2. Laboratory of Medical Genetics, Central South University, Changsha, 410008, Hunan, People's Republic of China. 3. Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, 410008, Hunan, People's Republic of China. 4. National Clinical Research Center for Geriatric Diseases, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People's Republic of China. 5. Department of Neurology, Xiangya Hospital, Central South University, 87 Xiangya Rd, Changsha, Hunan, People's Republic of China. junling.wang@csu.edu.cn. 6. Laboratory of Medical Genetics, Central South University, Changsha, 410008, Hunan, People's Republic of China. junling.wang@csu.edu.cn. 7. Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, 410008, Hunan, People's Republic of China. junling.wang@csu.edu.cn. 8. National Clinical Research Center for Geriatric Diseases, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People's Republic of China. junling.wang@csu.edu.cn.
Abstract
BACKGROUND: Spinocerebellar ataxia type 8 (SCA8) is a rare autosomal dominant neurodegenerative disease caused by CTA/CTG repeat expansion in the ATXN8/ATXN8OS gene. METHODS: To analyze the frequency and clinical characteristics of SCA8 patients in mainland China, we combined polymerase chain reaction (PCR) and triplet repeat-primed PCR (TRP-PCR) to detect the CTA/CTG expansion. We studied a cohort of 362 ataxia patients in which the other known causative genes had been previously excluded, from among 1294 index patients. Positive samples were validated by southern blotting. RESULTS: The CTA/CTG expansion was observed in six probands, accounting for approximately 0.46% (6/1294) in all patients, and 1.66% (6/362) in patients without definite molecular diagnosis. Clinically, aside from the typical SCA8 phenotype, some patients carrying the CTA/CTG expansion exhibited the cerebellar form of multisystem atrophy (MSA-C) and ataxia with paroxysmal kinesigenic dyskinesia (PKD). CONCLUSION: For the first time, we described the PKD phenotype in association with CTA/CTG expansion, suggesting that CTA/CTG expansion might play a role in the pathogenesis of paroxysmal dyskinesia symptoms.
BACKGROUND:Spinocerebellar ataxia type 8 (SCA8) is a rare autosomal dominant neurodegenerative disease caused by CTA/CTG repeat expansion in the ATXN8/ATXN8OS gene. METHODS: To analyze the frequency and clinical characteristics of SCA8patients in mainland China, we combined polymerase chain reaction (PCR) and triplet repeat-primed PCR (TRP-PCR) to detect the CTA/CTG expansion. We studied a cohort of 362 ataxiapatients in which the other known causative genes had been previously excluded, from among 1294 index patients. Positive samples were validated by southern blotting. RESULTS: The CTA/CTG expansion was observed in six probands, accounting for approximately 0.46% (6/1294) in all patients, and 1.66% (6/362) in patients without definite molecular diagnosis. Clinically, aside from the typical SCA8 phenotype, some patients carrying the CTA/CTG expansion exhibited the cerebellar form of multisystem atrophy (MSA-C) and ataxia with paroxysmal kinesigenic dyskinesia (PKD). CONCLUSION: For the first time, we described the PKD phenotype in association with CTA/CTG expansion, suggesting that CTA/CTG expansion might play a role in the pathogenesis of paroxysmal dyskinesia symptoms.
Entities:
Keywords:
ATXN8/ATXN8OS; Cerebellar form of multisystem atrophy (MSA-C); Paroxysmal kinesigenic dyskinesia (PKD); Spinocerebellar ataxia type 8 (SCA8); Trinucleotide repeat expansion
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