Evidence and practices of the use of next generation sequencing in patients with undiagnosed autosomal dominant cerebellar ataxias: a review

ABSTRACT Autosomal dominant cerebellar ataxias (ADCA) are heterogeneous diseases with a highly variable phenotype and genotype. They can be divided into episodic ataxia and spinocerebellar ataxia (SCA); the latter is considered the prototype of the ADCA. Most of the ADCA are caused by polyglutamine expansions, mainly SCA 1, 2, 3, 6, 7, 17 and Dentatorubral-pallidoluysian atrophy (DRPLA). However, 30% of patients remain undiagnosed after testing for these most common SCA. Recently, several studies have demonstrated that the new generation of sequencing methods are useful for the diagnose of these patients. This review focus on searching evidence on the literature, its usefulness in clinical practice and future perspectives.

摘要：常染色体显性遗传性小脑共济失调（Autosomal dominant cerebellar ataxias, ADCA）是一类表型与基因型均具有高度异质性的疾病。该类疾病可分为发作性共济失调与脊髓小脑共济失调（Spinocerebellar ataxia, SCA）两类，其中脊髓小脑共济失调被认为是ADCA的原型疾病。多数ADCA由多聚谷氨酰胺扩增所致，常见亚型包括SCA 1、2、3、6、7、17型以及齿状核红核苍白球路易体萎缩症（Dentatorubral-pallidoluysian atrophy, DRPLA）。然而，针对上述常见SCA亚型完成检测后，仍有30%的患者未能获得明确诊断。近年来多项研究表明，新一代测序技术可有效助力此类未确诊患者的诊断工作。本综述旨在系统梳理现有文献中的相关证据，探讨其在临床实践中的应用价值，并展望未来的研究前景。