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 ca..