Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
Institute for Molecular and Cell Biology, University of Porto, Porto, Portugal.
Epilepsia. 2023 Jun;64 Suppl 1:S22-S30. doi: 10.1111/epi.17593. Epub 2023 Apr 4.
In recent years, a large group of familial epilepsies and hereditary ataxias have emerged, caused by an extraordinary type of a novel pentanucleotide repeat expansion that has arisen in a preexisting nonpathogenic repeat tract. Remarkably, these insertions have occurred in noncoding regions of genes expressed in the cerebellum, but with highly diverse functions. These conditions, clinically very heterogeneous, may remain underdiagnosed in patients with atypical phenotypes and age at onset. They share, however, many genetic and phenotypic features, and discovery or detection of their pathogenic pentanucleotide repeats for diagnostic purposes can be achieved using recent bioinformatic methods. Here, we focus on the latest advances regarding the peculiar group of pentanucleotide repeat-related disorders beyond epilepsies.
近年来,大量的家族性癫痫和遗传性共济失调已经出现,这是由一种特殊类型的新型五核苷酸重复扩展引起的,这种扩展出现在先前存在的非致病性重复片段中。值得注意的是,这些插入发生在小脑表达的基因的非编码区域,但具有高度多样化的功能。这些情况在临床表现非常异质的患者中可能被漏诊,且发病年龄也各不相同。然而,它们具有许多遗传和表型特征,并且可以使用最近的生物信息学方法发现或检测其致病性五核苷酸重复以用于诊断目的。在这里,我们专注于除癫痫以外的五核苷酸重复相关疾病的最新进展。