A diagnostic ceiling for exome sequencing in cerebellar ataxia and related neurological disorders.

ABSTRACT: Genetic ataxias are associated with mutations in hundreds of genes with high phenotypic overlap complicating the clinical diagnosis. Whole-exome sequencing (WES) has increased the overall diagnostic rate considerably. However, the upper limit of this method remains ill-defined, hindering efforts to address the remaining diagnostic gap. To further assess the role of rare coding variation in ataxic disorders, we reanalyzed our previously published exome cohort of 76 predominantly adult and sporadic-onset patients, expanded the total number of cases to 260, and introduced analyses for copy number variation and repeat expansion in a representative subset. For new cases (n = 184), our resulting clinically relevant detection rate remained stable at 47% with 24% classified as pathogenic. Reanalys

SUBMITTER: Ngo KJ 

PROVIDER: S-EPMC7182470 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature