{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Theis JL"],"funding":["Todd and Karen Wanek Family Program for Hypoplastic Left Heart Syndrome at Mayo Clinic Foundation","NIA NIH HHS","NHLBI NIH HHS","National Institutes of Health","NIH HHS"],"pagination":["e59554"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7581429"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["9"],"pubmed_abstract":["Congenital heart diseases (CHDs), including hypoplastic left heart syndrome (HLHS), are genetically complex and poorly understood. Here, a multidisciplinary platform was established to functionally evaluate novel CHD gene candidates, based on whole-genome and iPSC RNA sequencing of a HLHS family-trio. Filtering for rare variants and altered expression in proband iPSCs prioritized 10 candidates. siRNA/RNAi-mediated knockdown in healthy human iPSC-derived cardiomyocytes (hiPSC-CM) and in developing <i>Drosophila</i> and zebrafish hearts revealed that LDL receptor-related protein <i>LRP2</i> is required for cardiomyocyte proliferation and differentiation. Consistent with hypoplastic heart defects, compared to patents the proband's iPSC-CMs exhibited reduced proliferation. Interestingly, rare,"],"journal":["eLife"],"pubmed_title":["Patient-specific genomics and cross-species functional analysis implicate LRP2 in hypoplastic left heart syndrome."],"pmcid":["PMC7581429"],"funding_grant_id":["HL054732","SAN-233970","R21 AG061598","R01 HL132241","R01 HL054732","R01 HL153645","R01 HL148827"],"pubmed_authors":["Bodmer R","Nelson TJ","Missinato MA","Walls SM","Colas AR","Theis JL","Martinez-Fernandez A","Zeng XI","Ocorr K","Fogarty ZC","Kezos JN","Olson TM","Vogler G","Birker K","Li X","Nielsen T","Evans JM","Grossfeld P","Terzic A","O'Byrne MM","Kervadec A"],"additional_accession":[]},"is_claimable":false,"name":"Patient-specific genomics and cross-species functional analysis implicate LRP2 in hypoplastic left heart syndrome.","description":"Congenital heart diseases (CHDs), including hypoplastic left heart syndrome (HLHS), are genetically complex and poorly understood. Here, a multidisciplinary platform was established to functionally evaluate novel CHD gene candidates, based on whole-genome and iPSC RNA sequencing of a HLHS family-trio. Filtering for rare variants and altered expression in proband iPSCs prioritized 10 candidates. siRNA/RNAi-mediated knockdown in healthy human iPSC-derived cardiomyocytes (hiPSC-CM) and in developing <i>Drosophila</i> and zebrafish hearts revealed that LDL receptor-related protein <i>LRP2</i> is required for cardiomyocyte proliferation and differentiation. Consistent with hypoplastic heart defects, compared to patents the proband's iPSC-CMs exhibited reduced proliferation. Interestingly, rare,","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Oct","modification":"2026-05-03T00:21:11.669Z","creation":"2020-10-29T15:57:25Z"},"accession":"S-EPMC7581429","cross_references":{"pubmed":["33006316"],"doi":["10.7554/eLife.59554"]}}