Open Access

ARTICLE

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

Nelly Sabbaghian¹, Maria C. Digilio², Gillian M. Blue^3,4, Timothée Revil⁵, David S. Winlaw^3,4, William D. Foulkes^1,6

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:

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.

---

Keywords

---