Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia.
Emerg Top Life Sci. 2023 Dec 14;7(3):349-359. doi: 10.1042/ETLS20230018.
Hereditary cerebellar ataxias are a heterogenous group of progressive neurological disorders that are disproportionately caused by repeat expansions (REs) of short tandem repeats (STRs). Genetic diagnosis for RE disorders such as ataxias are difficult as the current gold standard for diagnosis is repeat-primed PCR assays or Southern blots, neither of which are scalable nor readily available for all STR loci. In the last five years, significant advances have been made in our ability to detect STRs and REs in short-read sequencing data, especially whole-genome sequencing. Given the increasing reliance of genomics in diagnosis of rare diseases, the use of established RE detection pipelines for RE disorders is now a highly feasible and practical first-step alternative to molecular testing methods. In addition, many new pathogenic REs have been discovered in recent years by utilising WGS data. Collectively, genomes are an important resource/platform for further advancements in both the discovery and diagnosis of REs that cause ataxia and will lead to much needed improvement in diagnostic rates for patients with hereditary ataxia.
遗传性小脑共济失调是一组异质性进行性神经系统疾病，主要由短串联重复（STR）的重复扩展（RE）引起。重复疾病（如共济失调）的基因诊断较为困难，因为目前的诊断金标准是重复引物 PCR 检测或 Southern 印迹，这两种方法都不具有可扩展性，也不能用于所有 STR 基因座。在过去五年中，我们在检测短读测序数据（尤其是全基因组测序）中的 STR 和 RE 的能力方面取得了重大进展。鉴于基因组学在罕见病诊断中的应用日益增加，使用已建立的 RE 检测管道来检测 RE 疾病，现在是替代分子检测方法的一种高度可行且实用的第一步。此外，近年来，利用 WGS 数据发现了许多新的致病性 RE。总的来说，基因组是发现和诊断导致共济失调的 RE 的重要资源/平台，将大大提高遗传性共济失调患者的诊断率。
