Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/30718
Title: Unexpected diagnosis of myotonic dystrophy type 2 repeat expansion by genome sequencing.
Austin Authors: Rafehi, Haloom;Green, Cherie;Bozaoglu, Kiymet;Gillies, Greta;Delatycki, Martin B ;Lockhart, Paul J;Scheffer, Ingrid E ;Bahlo, Melanie
Affiliation: Department of Medical Biology, University of Melbourne, Melbourne, VIC, Australia..
Bruce Lefroy Centre for Genetic Health Research, Murdoch Children's Research Institute, Melbourne, VIC, Australia..
Medicine (University of Melbourne)
Department of Paediatrics, The University of Melbourne, Melbourne, VIC, Australia..
The Florey Institute of Neuroscience and Mental Health
Murdoch Children's Research Institute, Melbourne, VIC, Australia..
Victorian Clinical Genetics Services, Melbourne, VIC, Australia..
The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia..
Department of Psychology and Counselling, School of Psychology and Public Health, La Trobe University, Melbourne, VIC, Australia..
The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia..
Issue Date: 2023
Date: 2022
Publication information: European Journal of Human Genetics : EJHG 2023; 31(1)
Abstract: Several neurological disorders, such as myotonic dystrophy are caused by expansions of short tandem repeats (STRs) which can be difficult to detect by molecular tools. Methodological advances have made repeat expansion (RE) detection with whole genome sequencing (WGS) feasible. We recruited a multi-generational family (family A) ascertained for genetic studies of autism spectrum disorder. WGS was performed on seven children from four nuclear families from family A and analyzed for REs of STRs known to cause neurological disorders. We detected an expansion of a heterozygous intronic CCTG STR in CNBP in two siblings. This STR causes myotonic dystrophy type 2 (DM2). The expansion did not segregate with the ASD phenotype. Repeat-primed PCR showed that the DM2 CCTG motif was expanded above the pathogenic threshold in both children and their mother. On subsequent examination, the mother had mild features of DM2. We show that screening of STRs in WGS datasets has diagnostic utility, both in the clinical and research domain, with potential management and genetic counseling implications.
URI: https://ahro.austin.org.au/austinjspui/handle/1/30718
DOI: 10.1038/s41431-022-01166-y
ORCID: http://orcid.org/0000-0002-0807-2813
http://orcid.org/0000-0003-2531-8413
http://orcid.org/0000-0002-2311-2174
http://orcid.org/0000-0001-5132-0774
http://orcid.org/0000-0002-8769-2569
Journal: European Journal of Human Genetics: EJHG
PubMed URL: 35945246
PubMed URL: https://pubmed.ncbi.nlm.nih.gov/35945246/
Type: Journal Article
Appears in Collections:Journal articles

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