Spinocerebellar ataxia (SCA) is a rare autosomal neurodegenerative disease. SCA28 is a rare subtype, caused by heterozygous mutation of the pathogenic gene AFG3L2. The clinical features usually include slowly progressive gait and limb ataxia, dysarthria, hyperreflexia of the lower limbs, gaze-evoked nystagmus, ptosis, ophthalmoplegia, decreased ankle reflex, Parkinsonism, dystonia and cognitive impairment. In this paper, a case of SCA28 with orthostatic tremor is reported. The gene detection showed that there was a missense mutation of c. 2098G>A in the AFG3L2 gene of the patient. The clinical symptoms and pathogenic gene mutations of 79 cases of SCA28 type in the previous relevant literature are summarized to strengthen the understanding and clinical diagnosis of the disease.
WANG Qunfeng, LIU Shihua. A case of spinocerebellar ataxia type 28 with orthostatic tremor. Journal of Shanghai Jiao Tong University (Medical Science)[J], 2023, 43(4): 514-518 doi:10.3969/j.issn.1674-8115.2023.04.016
Note：A. Family diagram of the proband. B. Missense mutation c.2098G>A (p.E700K) in the proband. C. Missense mutation c.2098G>A (p.E700K) in the proband's mother. D. Conservative analysis of different species.
Fig 2
Pedigree of the proband and AFG3L2 Sanger sequencing diagram
1.3 基因测序
抽取先证者外周血样本，采用重复引物PCR（repeat-primed PCR，RP-PCR）和毛细管电泳技术筛查和排除了SCA1、2、3、6、7、8、10、12、17、36，以及齿状核红核苍白球路易体萎缩症（dentatorubrar-pallidoluysian atrophy，DRPLA）和弗里德赖希共济失调（Friedreich ataxia，FRDA）的动态突变。为了明确先证者的致病基因，对先证者外周血DNA进行全外显子组基因测序，结果显示AFG3L2基因（chr18：12337417）存在c.2098G>A（p.E700K）错义突变（图2B）。筛选先证者和其母亲的AFG3L2基因进行Sanger测序和家系共分离，结果显示AFG3L2基因是致病基因（图2C）。突变位点在不同物种间是非常保守的（图2D）。根据美国医学遗传学与基因组学会（American College of Medical Genetics and Genomics，ACMG）指南，变异c.2098G>A（p.E700K）被评为“可能致病”。结合患者临床特征和基因检测结果，诊断该病为SCA28。先证者接受了对症支持药物治疗，其母亲未接受任何治疗。2例患者共济失调症状持续恶化。
The paper was designed by LIU Shihua. The clinical data of the patient was collected by WANG Qunfeng and LIU Shihua. The manuscript was drafted and revised by WANG Qunfeng. Both authors have read the last version of paper and consented for submission.
利益冲突声明
所有作者声明不存在利益冲突。
COMPETING INTERESTS
Both authors disclose no relevant conflict of interests.
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