Rare Forms of Autosomal Recessive Spinocerebellar Ataxia Associated with Mutations in the ANO10 (ATX-ANO10) and SYNE1 (ATX-SYNE1) Genes
摘要
Objective. To analyze the clinical and genetic characteristics of patients with confirmed diagnoses of rare forms of autosomal recessive spinocerebellar ataxia – ATX-ANO10 and ATX-SYNE1. Materials and methods. Six unrelated patients with established diagnoses were examined, four with ATX-ANO10 and two with ATX-SYNE1. Brain MRI, nerve conduction study , assessment of the main neurological symptoms on the Scale for the Assessment and Rating of Ataxia (SARA), and screening for cognitive impairment on the Monreal Cognitive Assessment Scale (MoCA) were performed. Screening for mutations included panel sequencing on the Illumina MiSeq platform. Results. Panel sequencing detected six nucleotide variants in the ANO10 gene: known pathogenic nonsense mutations c.G1025A (p.W342X) and c.C1244G (p.S415X), likely pathogenic variants c.1477–2A>G and c.G101T (p.W34L), described by us for the first time, as well as missense mutations c.A110C (p.N37T) and c.T104C (p.L35P) of uncertain significance. In the SYNE1 gene, the previously undescribed nonsense mutation c.C8911T (p.Q2971X) and the known pathogenic substitution c.C4939T (p.Q1647X) were detected. The clinical picture of ATX-ANO10 and ATX-SYNE1 was typical, consisting of slowly progressive cerebellar ataxia with pyramidal syndrome, with onset at a young age and cerebellar atrophy seen on brain MRI scans. Conclusions. We report here the first data on the clinical features and spectrum of mutations in Russian patients with ATX-ANO10 and ATX-SYNE1 ataxias. The phenotypes of these diseases were nonspecific, so massive parallel sequencing is the method of choice for DNA diagnostics.