Whole genome sequencing delineates regulatory, structural, and cryptic splice variants in early onset cardiomyopathy
|Study ID||Alternative Stable ID||Type|
Cardiomyopathy (CMP) is a heritable disorder. Over 50% 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 1,953 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 % 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 % harbored high-risk regulatory variants in promoters and enhancers of CMP genes (Odds ratio 2.25, p=6.70×10-7 versus 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 ... (Show More)
Study Datasets 1 dataset.
Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data
Whole genome sequencing of 209 pediatric probands with primary cardiomyopathy and their family members. All samples were sequenced using Illumina short read platform.
|HiSeq X Ten||114|
Who archives the data?