Abstract
Background Spinocerebellar ataxias (SCA) are often caused by expansions of short tandem repeats (STRs). Recent methodological advances have made repeat expansion (RE) detection with whole genome sequencing (WGS) feasible.
Objectives To determine the genetic basis of ataxia in a multigenerational Australian pedigree, with autosomal dominant inheritance.
Methods and Results WGS was performed on three affected relatives. The sequence data was screened for known pathogenic REs using two repeat expansion detection tools: exSTRa and ExpansionHunter. This screen provided a clear and rapid diagnosis (<five days from receiving the sequencing data) of SCA36, a rare form of ataxia caused by an intronic GGCCTG RE in NOP56.
Conclusions the that diagnosis of rare ataxias caused by REs is highly feasible and cost effective with WGS. We propose that WGS be implemented as the frontline, cost effective methodology for molecular testing of individuals with a clinical diagnosis of ataxia.
Footnotes
Financial disclosure/conflicts of interest: Nothing to report.
Funding sources for study: The funding bodies had no role in the design, analysis, interpretation or reporting of results.
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