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Analysis of DICER1 in familial and sporadic cases of transposition of the great arteries

Nelly Sabbaghian1, Maria C. Digilio2, Gillian M. Blue3,4, Timothée Revil5, David S. Winlaw3,4, William D. Foulkes1,6

1 Lady Davis Institute, Segal Cancer Centre, Jewish General Hospital, Montreal, Quebec, Canada
2 Department of Medical Genetics, Bambino Gesu Pediatric Hospital, Rome, Italy
3 Heart Centre for Children, The Children’s Hospital at Westmead, Westmead, New South Wales, Australia
4 University of Sydney, Sydney, New South Wales, Australia
5 McGill University and Genome Quebec Innovation Centre, Montreal, Quebec, Canada
6 Cancer Research Program, Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec, Canada

* Corresponding Author: William D. Foulkes, Research Institute of the McGill University Health Centre, 1001 Decarie Boulevard, Montreal, Room EM0.6248, Quebec H4A 3J1, Canada. Email: email

Congenital Heart Disease 2018, 13(3), 401-406. https://doi.org/10.1111/chd.12578

Abstract

Objective: We previously identified a pathogenic germline DICER1 variant in a child with transposition of the great arteries who was a member of a family with DICER1 syndrome. In view of a report linking DICER1 knockout in murine cardiomyocytes to cardiac outflow defects, we investigated the involvement of DICER1 in transposition of the great arteries.
Design: We used Fluidigm access array followed by next generation sequencing to screen for variants in the coding exons, their exon/intron boundaries and the 30 untranslated region of DICER1 in patient DNA.
Cases: Germline DNA was collected from 129 patients with either sporadic or familial forms of transposition of the great arteries from two sites in Australia and Italy.
Results: Most cases (85%) did not have any germline DICER1 variants. In the remaining 15% of cases, we identified 16 previously reported variants (5 synonymous, 6 intronic, and 5 missense) and 2 novel variants (1 intronic and 1 missense). None of the identified variants were predicted to be pathogenic.
Conclusions: Here, we report that neither likely pathogenic nor pathogenic variants in DICER1 appear to play a major role in transposition of the great arteries.

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Cite This Article

Sabbaghian, N., Digilio, M. C., Blue, G. M., Revil, T., Winlaw, D. S. et al. (2018). Analysis of DICER1 in familial and sporadic cases of transposition of the great arteries. Congenital Heart Disease, 13(3), 401–406. https://doi.org/10.1111/chd.12578



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