Unexpected diagnosis of myotonic dystrophy type 2 repeat expansion by genome sequencing

H Rafehi; C Green; K Bozaoglu; G Gillies; MB Delatycki; PJ Lockhart; IE Scheffer; M Bahlo

Journal article

Unexpected diagnosis of myotonic dystrophy type 2 repeat expansion by genome sequencing

H Rafehi, C Green, K Bozaoglu, G Gillies, MB Delatycki, PJ Lockhart, IE Scheffer, M Bahlo

European Journal of Human Genetics | SPRINGERNATURE | Published : 2023

DOI: 10.1038/s41431-022-01166-y

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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 segreg..

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University of Melbourne Researchers

Haloom Rafehi Author

Kiymet Bozaoglu Author

Martin Delatycki Author

Paul Lockhart Author

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Awarded by National Health and Medical Research Council

Funding Acknowledgements

This work was funded in part by National Health and Medical Research Council of Australia Project Grants (GNT1044175 and GNT1098255). HR was supported by an NHMRC EL1 Investigator Grant (GNT1194364). KB was supported by an EH Flack Fellowship. IES was supported by a NHMRC Senior Practitioner Fellowship (GNT1006110; GNT1104831). PJL was supported by a NHMRC Fellowship (GNT1032364) and the Vincent Chiodo Foundation. MB was supported by an NHMRC Senior Research Fellowship (GNT1102971). This work was made possible through the Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS.