{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"technology_type":["Illumina HiSeq 2000"],"study_type":["Other"],"full_dataset_link":["https://ega-archive.org/studies/EGAS00001000317"],"host":["EGA"],"description":["EGA study EGAS00001000317"],"dataset_title":["Exome sequencing of Congenital Heart Disease families Toronto"],"repository":["EGA"],"category":["restricted"],"pubmed_abstract":["Congenital heart defects (CHDs) are the most common birth defect worldwide and are a leading cause of neonatal mortality. Nonsyndromic atrioventricular septal defects (AVSDs) are an important subtype of CHDs for which the genetic architecture is poorly understood. We performed exome sequencing in 13 parent-offspring trios and 112 unrelated individuals with nonsyndromic AVSDs and identified five rare missense variants (two of which arose de novo) in the highly conserved gene NR2F2, a very significant enrichment (p = 7.7 × 10(-7)) compared to 5,194 control subjects. We identified three additional CHD-affected families with other variants in NR2F2 including a de novo balanced chromosomal translocation, a de novo substitution disrupting a splice donor site, and a 3 bp duplication that cosegregated in a multiplex family. NR2F2 encodes a pleiotropic developmental transcription factor, and decreased dosage of NR2F2 in mice has been shown to result in abnormal development of atrioventricular septa. Via luciferase assays, we showed that all six coding sequence variants observed in individuals significantly alter the activity of NR2F2 on target promoters."],"pubmed_title":["Rare variants in NR2F2 cause congenital heart defects in humans."],"pubmed_authors":["Al Turki Saeed S, Manickaraj Ashok K AK, Mercer Catherine L CL, Gerety Sebastian S SS, Hitz Marc-Phillip MP, Lindsay Sarah S, D'Alessandro Lisa C A LC, Swaminathan G Jawahar GJ, Bentham Jamie J, Arndt Anne-Karin AK, Louw Jacoba J, Low Jacoba J, Breckpot Jeroen J, Gewillig Marc M, Gewillig Marc M, Thienpont Bernard B, Abdul-Khaliq Hashim H, Harnack Christine C, Hoff Kirstin K, Kramer Hans-Heiner HH, Schubert Stephan S, Siebert Reiner R, Toka Okan O, Cosgrove Catherine C, Watkins Hugh H, Lucassen Anneke M AM, O'Kelly Ita M IM, Salmon Anthony P AP, Bu'lock Frances A FA, Granados-Riveron Javier J, Setchfield Kerry K, Thornborough Chris C, Brook J David JD, Mulder Barbara B, Klaassen Sabine S, Bhattacharya Shoumo S, Devriendt Koen K, Fitzpatrick David F DF, Wilson David I DI, Mital Seema S, Hurles Matthew E ME"],"additional_accession":[]},"is_claimable":false,"name":"Exome sequencing of Congenital Heart Disease families Toronto","description":"Atrio-ventricular septal defects (AVSD) are a specific form of congenital heart structural defect that result from abnormal or inadequate fusion of endocardial cushions during cardiac development. This project is focused on identifying rare coding variation that substantially increases risk of AVSD, by exome sequencing of AVSD patients and some of their family members, and comparing to control datasets from other sources.","dates":{"updated":"2021-04-23 20:10:07"},"accession":"EGAS00001000317","cross_references":{"TAXONOMY":["9606"],"pubmed":["24702954"],"EGA":["EGAD00001000799","EGAC00001000205"]}}