{"id":7832,"date":"2026-01-30T17:00:19","date_gmt":"2026-01-30T17:00:19","guid":{"rendered":"http:\/\/sebigec.es\/blog\/?guid=13a610e34b18d385d0b2a14c6de7802a"},"modified":"2026-03-20T14:40:24","modified_gmt":"2026-03-20T14:40:24","slug":"expanding-the-phenotypic-spectrum-of-mecom-associated-syndrome-rare-variants-are-associated-with-syndromic-pulmonary-arterial-hypertension","status":"publish","type":"post","link":"https:\/\/sebigec.es\/blog\/index.php\/2026\/01\/30\/expanding-the-phenotypic-spectrum-of-mecom-associated-syndrome-rare-variants-are-associated-with-syndromic-pulmonary-arterial-hypertension\/","title":{"rendered":"Expanding the phenotypic spectrum of MECOM-associated syndrome: rare variants are associated with syndromic pulmonary arterial hypertension"},"content":{"rendered":"\n<sec><st>Background<\/st>\n<p>  <I>MECOM<\/I> encodes a developmental and haematopoietic transcription factor associated with a rare early-onset syndrome including bone marrow failure, skeletal and other congenital anomalies. Heterozygous de novo variants are the primary cause. We previously identified <I>MECOM<\/I> as a candidate gene for paediatric pulmonary arterial hypertension (PAH) using trio exome sequencing.<\/p>\n<\/sec>\n<sec><st>Methods<\/st>\n<p>To test the role of <I>MECOM<\/I> in paediatric PAH and further define the clinical phenotype of <I>MECOM<\/I>-associated syndrome, we queried GeneMatcher and screened rare disease databases for individuals with predicted deleterious <I>MECOM<\/I> variants. We analysed the clinical spectrum of patients, performed protein modelling of genetic variants and assessed cardiopulmonary expression.<\/p>\n<\/sec>\n<sec><st>Results<\/st>\n<p>We identified 15 individuals with <I>MECOM<\/I> variants, including 11 unrelated probands and 8 de novo variants. 11 individuals had severe or mild thrombocytopenia, 9 had skeletal issues, 8 had cardiac anomalies, 6 had PAH and 10 had additional conditions. Three were diagnosed in utero and died in the neonatal period. All missense variants map to the zinc finger 6 or zinc finger 8\/9 region, a known hotspot for <I>MECOM<\/I>-associated syndrome. Protein modelling predicted that both regions are DNA-binding, and that the variants may interfere with binding to a <I>VEGFR2<\/I>\/<I>KDR<\/I> enhancer. Data from LungMAP showed that <I>MECOM<\/I> is primarily expressed in pulmonary arterial endothelial cells.<\/p>\n<\/sec>\n<sec><st>Conclusion<\/st>\n<p>Rare <I>MECOM<\/I> variants are associated with early-onset syndromic PAH. PAH monitoring should be considered for all individuals with rare <I>MECOM<\/I> variants. We speculate that the pathogenetic mechanism for PAH and cardiac defects may be impaired <I>VEGFR2<\/I>\/<I>KDR<\/I> signalling.<\/p>\n<\/sec>\n","protected":false},"excerpt":{"rendered":"<p>Background<br \/>\n  MECOM encodes a developmental and haematopoietic transcription factor associated with a rare early-onset syndrome including bone marrow failure, skeletal and other congenital anomalies. Heterozygous de novo variants are the primary cause&#8230;.<\/p>\n","protected":false},"author":0,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[6,14],"tags":[83],"class_list":["post-7832","post","type-post","status-publish","format-standard","hentry","category-articulos","category-jmg","tag-jmedgenet"],"_links":{"self":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/7832","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/types\/post"}],"replies":[{"embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/comments?post=7832"}],"version-history":[{"count":2,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/7832\/revisions"}],"predecessor-version":[{"id":13113,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/7832\/revisions\/13113"}],"wp:attachment":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/media?parent=7832"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/categories?post=7832"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/tags?post=7832"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}