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）是一类兼具高度表型与遗传异质性的疾病，可划分为发作性共济失调与脊髓小脑共济失调（spinocerebellar ataxia, SCA）两大亚型，其中脊髓小脑共济失调被视为该类疾病的原型代表。绝大多数此类疾病由多谷氨酰胺扩增引发，以SCA1、2、3、6、7、17型及齿状核红核苍白球路易体萎缩症（Dentatorubral-pallidoluysian atrophy, DRPLA）最为常见。然而，仍有30%的患者在针对上述常见脊髓小脑共济失调亚型完成检测后仍未获得明确诊断。近年来多项研究表明，新一代测序技术可有效辅助此类患者的确诊工作。本综述旨在系统梳理相关文献证据，探讨其在临床实践中的应用价值，并展望未来研究前景。