Genetic landscape remodelling in spinocerebellar ataxias: the influence of next-generation sequencing

摘要: Hereditary cerebellar ataxias (HCAs) are clinically and genetically heterogeneous neurodegenerative disorders, characterised by a syndrome other neurological or non-neurological signs. So far, more than 20 genes have been described in autosomal dominant HCA; recessive HCA, even involved, often complex phenotypes. Because of that complexity, the genetic diagnosis these diseases is based on next-generation sequencing techniques. In this review paper, we discuss major contributions they made to landscape HCAs. Numerous novel identified; still recently implicated HCAs addition being responsible for diseases. The phenotypic spectrum associated with single gene constantly gains complexity. Novel types mutations transmissions known regularly identified. All factors make genotype–phenotype correlations particularly difficult. Some but not all variability can be explained different pathophysiological consequences (loss function, gain variable levels haploinsufficiency). This also raises question modifier genes. Finally, highlight some functional pathways increasingly appear important