Rapid Diagnosis of Spinocerebellar Ataxia 36 in a Three‐Generation Family Using Short‐Read Whole‐Genome Sequencing Data

Abstract Background Spinocerebellar ataxias are often caused by expansions of short tandem repeats. Recent methodological advances have made repeat expansion (RE) detection with whole‐genome sequencing (WGS) feasible. Objectives The objective of this study was to determine the genetic basis of ataxia in a multigenerational Australian pedigree with autosomal‐dominant inheritance. Methods and Results WGS was performed on 3 affected relatives. The sequence data were screened for known pathogenic REs using 2 RE detection tools: exSTRa and ExpansionHunter. This screen provided a clear and rapid diagnosis (<5 days from receiving the sequencing data) of spinocerebellar ataxia 36, a rare form of ataxia caused by an intronic GGCCTG RE in NOP56 . Conclusions The diagnosis of rare ataxias caused by REs is highly feasible and cost‐effective with WGS. We propose that WGS could potentially be implemented as the frontline, cost‐effective methodology for the molecular testing of individuals with a clinical diagnosis of ataxia. © 2020 International Parkinson and Movement Disorder Society