Kathleen Delfosse
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Research Subjects
Kathleen Delfosse has a total of 36 co-authors. Here are the top co-authors by number of shared publications:
- Abdelrahman Said
Genetics and Genome Biology Program, The Hospital For Sick Children, Toronto, Canada
1 shared publication Anastasia Miron
Genetics and Genome Biology Program, The Hospital For Sick Children, Toronto, Canada
1 shared publication- Bhooma Thiruvahindrapuram
The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Canada
1 shared publication - Christopher Semsarian
Agnes Ginges Centre for Molecular Cardiology at Centenary Institute (C.S.), The University of Sydney, New South Wales, Australia
1 shared publication - Erwin Oechslin
Toronto Adult Congenital Heart Disease Program, Division of Cardiology, Peter Munk Cardiac Centre, University Health Network, and University of Toronto, Toronto, Canada
1 shared publication Fintan McKenna
Genetics and Genome Biology Program, The Hospital For Sick Children, Toronto, Canada
1 shared publication
Latest Publications
- Open Access
- 14 March 2022
- Published by Springer Nature in npj Genomic Medicine
- Vol. 7 (1) , 1-17
Whole genome sequencing delineates regulatory, copy number, and cryptic splice variants in early onset cardiomyopathy
Cardiomyopathy (CMP) is a heritable disorder. Over 50% of cases are gene-elusive on clinical gene panel testing. The contribution of variants in non-coding DNA elements that result in cryptic splicing and regulate gene expression has not been explored. We analyzed whole-genome sequencing (WGS) data in a discovery cohort of 209 pediatric CMP patients and 1953 independent replication genomes and exomes. We searched for protein-coding variants, and non-coding variants predicted to affect the function or expression of genes. Thirty-nine percent of cases harbored pathogenic coding variants in known CMP genes, and 5% harbored high-risk loss-of-function (LoF) variants in additional candidate CMP genes. Fifteen percent harbored high-risk regulatory variants in promoters and enhancers of CMP genes (odds ratio 2.25,p = 6.70 × 10−7versus controls). Genes involved in α-dystroglycan glycosylation (FKTN,DTNA) and desmosomal signaling (DSC2,DSG2) were most highly enriched for regulatory variants (odds ratio 6.7–58.1). Functional effects were confirmed in patient myocardium and reporter assays in human cardiomyocytes, and in zebrafish CRISPR knockouts. We provide strong evidence for the genomic contribution of functionally active variants in new genes and in regulatory elements of known CMP genes to early onset CMP.
- 14 March 2022
- Published by Springer Nature in npj Genomic Medicine
- Vol. 7 (1) , 1-17
Open AccessWhole genome sequencing delineates regulatory, copy number, and cryptic splice variants in early onset cardiomyopathy
Cardiomyopathy (CMP) is a heritable disorder. Over 50% of cases are gene-elusive on clinical gene panel testing. The contribution of variants in non-coding DNA elements that result in cryptic splicing and regulate gene expression has not been explored. We analyzed whole-genome sequencing (WGS) data in a discovery cohort of 209 pediatric CMP patients and 1953 independent replication genomes and exomes. We searched for protein-coding variants, and non-coding variants predicted to affect the function or expression of genes. Thirty-nine percent of cases harbored pathogenic coding variants in known CMP genes, and 5% harbored high-risk loss-of-function (LoF) variants in additional candidate CMP genes. Fifteen percent harbored high-risk regulatory variants in promoters and enhancers of CMP genes (odds ratio 2.25,p = 6.70 × 10−7versus controls). Genes involved in α-dystroglycan glycosylation (FKTN,DTNA) and desmosomal signaling (DSC2,DSG2) were most highly enriched for regulatory variants (odds ratio 6.7–58.1). Functional effects were confirmed in patient myocardium and reporter assays in human cardiomyocytes, and in zebrafish CRISPR knockouts. We provide strong evidence for the genomic contribution of functionally active variants in new genes and in regulatory elements of known CMP genes to early onset CMP.