Original Article
Clinical characteristics and genetic analysis of cerebellar spinal ataxia type 8
Tao Jianxia, Guo Shuo, Zhou Yanbing, Wang Minjin, Zhou Yi
Published 2021-06-15
Cite as Int J Genet, 2021, 44(3): 146-151. DOI: 10.3760/cma.j.cn231536-20200923-00093
Abstract
ObjectiveSpinocerebellar ataxia type 8 (spinocerebellar ataxia 8, SCA8) is a slowly progressive ataxia caused by the abnormal repeated expansion of CTA/CTG in the non-coding region of the pathogenic gene ATXN8OS.Recently, the proportion of SCA8 in Chinese patients with SCA has increased.This study focused on the distribution of ATXN8OS gene(CTA/CTG)n expansion mutation in SCA patients in mainland of China, and detailed the clinical features of SCA8 patients and compared them with the most common clinical features of SCA3 patients in SCA.
MethodsFluorescence PCR and capillary gel electrophoresis were used to analyze the trinucleotide repeats of ATXN8OS gene in 700 patients with unknown typing of SCA(excluding SCA1, SCA2, SCA3, SCA6, SCA7, SCA12, SCA17 and globus pallidus atrophy of dentate nucleus), and the clinical data of the patients were collected, which included 57 patients with SCA3.
ResultsThe(CTA/CTG)n nucleotide extension mutations of ATXN8OS gene was found in three patients with SCA, one of them completed the pedigree follow-up at the later stage, and the other two patients were sporadic cases[one of which had clinical features of multiple system atrophy MSA)]. Among the other 697 SCA patients, the variation range of ATXN8OS gene(CTA/CTG)n was 4 ~ 69, and the average number of repeats was 21.17±7.49, 18 repeats were the most common, and 144 homozygotes were found.The homozygous rate was 20.7%.There was no significant difference between SCA8 and SCA3 in clinic, but both had pyramidal and extrapyramidal signs and cerebellar atrophy.
ConclusionThe distribution of(CTA/CTG)n copy number of ATXN8OS gene in the Chinese population is low as a whole.SCA8 is not rare in China.The extended mutation of(CTA/CTG)n in the ATXN8OS gene is unstable and may change in the process of inheritance.The age of onset of SCA8 is later than that of SCA3, but the clinical manifestations of patients are similar, and MSA may be one of the atypical symptoms of SCA8.Therefore, the analysis of trinucleotide repeats of the ATXN8OS gene in patients with suspected SCA or MSA is of great significance for clinical diagnosis and treatment.
Key words:
Spinocerebellar ataxia; SCA8; SCA3; Differential diagnosis
Contributor Information
Tao Jianxia
Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, China
Guo Shuo
Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, China
Zhou Yanbing
Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, China
Wang Minjin
Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, China
Zhou Yi
Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, China
