Fogel Brent L
Program in Neurogenetics, Departments of Neurology and Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, United States.
Handb Clin Neurol. 2018;147:187-209. doi: 10.1016/B978-0-444-63233-3.00013-0.
The autosomal-recessive cerebellar ataxias comprise more than half of the known genetic forms of ataxia and represent an extensive group of clinically heterogeneous disorders that can occur at any age but whose onset is typically prior to adulthood. In addition to ataxia, patients often present with polyneuropathy and clinical symptoms outside the nervous system. The most common of these diseases is Friedreich ataxia, caused by mutation of the frataxin gene, but recent advances in genetic analysis have greatly broadened the ever-expanding number of causative genes to over 50. In this review, the clinical neurogenetics of the recessive cerebellar ataxias will be discussed, including updates on recently identified novel ataxia genes, advancements in unraveling disease-specific molecular pathogenesis leading to ataxia, potential treatments under development, technologic improvements in diagnostic testing such as clinical exome sequencing, and what the future holds for clinicians and geneticists.
常染色体隐性遗传性小脑共济失调占已知遗传性共济失调形式的一半以上，是一组广泛的临床异质性疾病，可发生于任何年龄，但通常在成年前发病。除共济失调外，患者常伴有多发性神经病及神经系统以外的临床症状。其中最常见的疾病是弗里德赖希共济失调，由铁调素基因突变引起，但基因分析的最新进展已极大地拓宽了致病基因的范围，目前已超过50种。在这篇综述中，将讨论隐性遗传性小脑共济失调的临床神经遗传学，包括最近发现的新共济失调基因的更新情况、揭示导致共济失调的疾病特异性分子发病机制的进展、正在研发的潜在治疗方法、诊断检测技术的改进（如临床外显子组测序），以及临床医生和遗传学家的未来展望。
