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Title: Rapid Diagnosis of Spinocerebellar Ataxia 36 in a three-Generation Family Using Short-Read Whole-Genome Sequencing Data.
Austin Authors: Rafehi, Haloom;Szmulewicz, David J;Pope, Kate;Wallis, Mathew;Christodoulou, John;White, Susan M;Delatycki, Martin B ;Lockhart, Paul J;Bahlo, Melanie
Affiliation: Murdoch Children's Research Institute, Parkville, Victoria, Australia
Brain and Mitochondrial Research Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia
Department of Pediatrics, The University of Melbourne, Parkville, Victoria, Australia
Victorian Clinical Genetics Services, Parkville, Victoria, Australia
Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia
Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia
Epilepsy Research Centre, Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Bruce Lefroy Centre for Genetic Health Research, Murdoch Children's Research Institute, Parkville, Victoria, Australia
Cerebellar Ataxia Clinic, Neuroscience Department, Alfred Health, Melbourne, Victoria, Australia
Balance Disorders and Ataxia Service, Royal Victorian Eye & Ear Hospital, East Melbourne, Victoria, Australia
Tasmanian Clinical Genetics Service, Tasmanian Health Service, Tasmania, Australia
School of Medicine and Menzies Institute for Medical Research, University of Tasmania, Tasmania, Australia
Issue Date: 14-May-2020
Date: 2020-05-14
Publication information: Movement Disorders 2020; 35(9): 1675-1679
Abstract: 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. The objective of this study was to determine the genetic basis of ataxia in a multigenerational Australian pedigree with autosomal-dominant inheritance. 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. 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.
DOI: 10.1002/mds.28105
ORCID: 0000-0003-2531-8413
Journal: Movement Disorders
PubMed URL: 32407596
Type: Journal Article
Subjects: ataxia
repeat expansions
short tandem repeats
Appears in Collections:Journal articles

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