Rapid diagnosis of Spinocerebellar ataxia 36 in a three-generation family using short-read whole-genome sequencing data
- Author(s)
- Rafehi, H; Szmulewicz, DJ; Pope, K; Wallis, M; Christodoulou, J; White, SM; Delatycki, MB; Lockhart, PJ; Bahlo, M;
- Journal Title
- Movement Disorders
- Publication Type
- Journal epub ahead of print
- 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. (c) 2020 International Parkinson and Movement Disorder Society.
- Publisher
- Wiley
- Research Division(s)
- Population Health And Immunity
- PubMed ID
- 32407596
- Publisher's Version
- https://doi.org/10.1002/mds.28105
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2020-05-18 11:15:18
Last Modified: 2020-05-18 11:58:38