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

Haloom Rafehi, David J. Szmulewicz, Kate Pope, Mathew Wallis, John Christodoulou, Susan M. White, Martin B. Delatycki, Paul J. Lockhart, Melanie Bahlo

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7 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1675-10679
Number of pages5
JournalMovement Disorders
Issue number9
Publication statusPublished - Sep 2020
Externally publishedYes


  • ataxia
  • diagnosis
  • exSTRa
  • repeat expansions
  • short tandem repeats

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