{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:21:35Z","timestamp":1790767295176,"version":"4.1.0"},"reference-count":19,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,7,22]],"date-time":"2019-07-22T00:00:00Z","timestamp":1563753600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R35 NS105078"],"award-info":[{"award-number":["R35 NS105078"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["UM1HG006542"],"award-info":[{"award-number":["UM1HG006542"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL137203"],"award-info":[{"award-number":["R01HL137203"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The canonical wingless (Wnt) and fibroblast growth factor (FGF) signaling pathways involving\n                    <jats:italic>CTNNB1<\/jats:italic>\n                    and\n                    <jats:italic>TBX4<\/jats:italic>\n                    , respectively, are crucial for the regulation of human development. Perturbations of these pathways and disruptions from biological homeostasis have been associated with abnormal morphogenesis of multiple organs, including the lung. The aim of this study was to identify the underlying genetic cause of abnormal lung growth, pulmonary hypertension (PAH), severe microcephaly, and muscle spasticity in a full\u2010term newborn, who died at 4\u2009months of age due to progressively worsening PAH and respiratory failure. Family trio exome sequencing showed a de novo heterozygous nonsense c.1603C&gt;T (p.Arg535*) variant in\n                    <jats:italic>CTNNB1<\/jats:italic>\n                    and a paternally inherited heterozygous missense c.1198G&gt;A (p.Glu400Lys) variant in\n                    <jats:italic>TBX4<\/jats:italic>\n                    , both predicted to be likely deleterious. We expand the phenotypic spectrum associated with\n                    <jats:italic>CTNNB1<\/jats:italic>\n                    and\n                    <jats:italic>TBX4<\/jats:italic>\n                    variants and indicate that they could act synergistically to produce a distinct more severe phenotype. Our findings further support a recently proposed complex compound inheritance model in lethal lung developmental diseases and the contention that dual molecular diagnoses can parsimoniously explain blended phenotypes.\n                  <\/jats:p>","DOI":"10.1111\/cge.13605","type":"journal-article","created":{"date-parts":[[2019,7,16]],"date-time":"2019-07-16T03:09:05Z","timestamp":1563246545000},"page":"366-370","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Heterozygous\n                    <i>CTNNB1<\/i>\n                    and\n                    <i>TBX4<\/i>\n                    variants in a patient with abnormal lung growth, pulmonary hypertension, microcephaly, and spasticity"],"prefix":"10.1111","volume":"96","author":[{"given":"Justyna A.","family":"Karolak","sequence":"first","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas"},{"name":"Department of Genetics and Pharmaceutical Microbiology Poznan University of Medical Sciences  Poznan Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Przemyslaw","family":"Szafranski","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Kilner","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Sleep Medicine Queensland Children's Hospital  South Brisbane Queensland Australia"},{"name":"The University of Queensland  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chirag","family":"Patel","sequence":"additional","affiliation":[{"name":"Genetic Health Queensland Royal Brisbane and Women's Hospital  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bonnie","family":"Scurry","sequence":"additional","affiliation":[{"name":"Pathology Queensland Royal Brisbane and Women's Hospital and Lady Cilento Children's Hospital  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Kinning","sequence":"additional","affiliation":[{"name":"West of Scotland Regional Genetics Service Queen Elizabeth Hospital  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Chandler","sequence":"additional","affiliation":[{"name":"Manchester Centre for Genomic Medicine, Saint Mary's Hospital Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalini N.","family":"Jhangiani","sequence":"additional","affiliation":[{"name":"Human Genome Sequencing Center Baylor College of Medicine  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeynep H.","family":"Coban Akdemir","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R.","family":"Lupski","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas"},{"name":"Human Genome Sequencing Center Baylor College of Medicine  Houston Texas"},{"name":"Texas Children's Hospital  Houston Texas"},{"name":"Department of Pediatrics Baylor College of Medicine  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwina","family":"Popek","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology Baylor College of Medicine  Houston 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