{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Machado RD"],"funding":["NIHR","British Heart Foundation","NIHR Cambridge Biomedical Research Centre","NHS Blood and Transplant","NHS","National Institute for Health Research (NIHR)","Special Project Grant and Personal Chair Award to NWM","Wellcome Trust","Academy of Medical Sciences","NHS Trusts"],"pagination":["906-911"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9411922"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["59(9)"],"pubmed_abstract":["<h4>Background</h4>The molecular genetic basis of pulmonary arterial hypertension (PAH) is heterogeneous, with at least 26 genes displaying putative evidence for disease causality. Heterozygous variants in the <i>ATP13A3</i> gene were recently identified as a new cause of adult-onset PAH. However, the contribution of <i>ATP13A3</i> risk alleles to child-onset PAH remains largely unexplored.<h4>Methods and results</h4>We report three families with a novel, autosomal recessive form of childhood-onset PAH due to biallelic <i>ATP13A3</i> variants. Disease onset ranged from birth to 2.5 years and was characterised by high mortality. Using genome sequencing of parent-offspring trios, we identified a homozygous missense variant in one case, which was subsequently confirmed to cosegregate with dis"],"journal":["Journal of medical genetics"],"pubmed_title":["Biallelic variants of <i>ATP13A3</i> cause dose-dependent childhood-onset pulmonary arterial hypertension characterised by extreme morbidity and mortality."],"pmcid":["PMC9411922"],"funding_grant_id":["204809/Z/16/Z","SBF005\\1115","BRC-1215-20014"],"pubmed_authors":["Debeljak M","Bleda M","Southgate L","Ekstein J","Hoover-Fong JE","Machado RD","Golden WC","Romer LH","NIHR Bioresource – Rare Diseases","Morrell NW","Hadinnapola C","Vesel S","Harris MA","Fineman JR","Hirsch Y","Welch CL","Coulson JD","Chung WK","Colglazier E","Griffin EL","Nogee L","Haimel M","Graf S"],"additional_accession":[]},"is_claimable":false,"name":"Biallelic variants of <i>ATP13A3</i> cause dose-dependent childhood-onset pulmonary arterial hypertension characterised by extreme morbidity and mortality.","description":"<h4>Background</h4>The molecular genetic basis of pulmonary arterial hypertension (PAH) is heterogeneous, with at least 26 genes displaying putative evidence for disease causality. Heterozygous variants in the <i>ATP13A3</i> gene were recently identified as a new cause of adult-onset PAH. However, the contribution of <i>ATP13A3</i> risk alleles to child-onset PAH remains largely unexplored.<h4>Methods and results</h4>We report three families with a novel, autosomal recessive form of childhood-onset PAH due to biallelic <i>ATP13A3</i> variants. Disease onset ranged from birth to 2.5 years and was characterised by high mortality. Using genome sequencing of parent-offspring trios, we identified a homozygous missense variant in one case, which was subsequently confirmed to cosegregate with dis","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Sep","modification":"2025-05-29T16:11:37.81Z","creation":"2025-04-04T09:32:19.981Z"},"accession":"S-EPMC9411922","cross_references":{"pubmed":["34493544"],"doi":["10.1136/jmedgenet-2021-107831"]}}