Skip to Main content Skip to Navigation
Journal articles

Multiallelic rare variants support an oligogenic origin of sudden cardiac death in the young

Abstract : Unexplained sudden death in the young is cardiovascular in most cases. Structural and conduction defects in cardiac-related genes can conspire to underlie sudden cardiac death. Here we report a clinical investigation and an extensive genetic assessment of a Tunisian family with sudden cardiac death in young members. In order to identify the family-genetic basis of sudden cardiac death, we performed Whole Exome Sequencing (WES), read depth copy-number-variation (CNV) screening and segregation analysis. We identify 6 ultra-rare pathogenic heterozygous variants in OBSCN, RYR2, DSC2, AKAP9, CACNA1C and RBM20 genes, and one homozygous splicing variant in TECRL gene consistent with an oligogenic model of inheritance. CNV analysis did not reveal any causative CNV consistent with the family phenotype. Overall, our results are highly suggestive for a cumulative effect of heterozygous missense variants as disease causation and to account for a greater disease severity among offspring. Our study further confirms the complexity of the inheritance of sudden cardiac death and highlights the utility of family-based WES and segregation analysis in the identification of family specific mutations within different cardiac genes pathways.
Complete list of metadata

https://hal-amu.archives-ouvertes.fr/hal-02965635
Contributor : Stéphane Zaffran Connect in order to contact the contributor
Submitted on : Wednesday, April 28, 2021 - 3:10:49 PM
Last modification on : Wednesday, November 3, 2021 - 5:49:52 AM
Long-term archiving on: : Thursday, July 29, 2021 - 6:54:13 PM

File

Hager et al.pdf
Files produced by the author(s)

Identifiers

Collections

Citation

Hager Jaouadi, Yosra Bouyacoub, Sonia Chabrak, Lilia Kraoua, Amira Zaroui, et al.. Multiallelic rare variants support an oligogenic origin of sudden cardiac death in the young. Herz, Springer Verlag, 2020, 46, pp.94-102. ⟨10.1007/s00059-019-04883-1⟩. ⟨hal-02965635⟩

Share

Metrics

Record views

81

Files downloads

151