{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T04:56:20Z","timestamp":1790571380249,"version":"4.1.0"},"reference-count":12,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>\n                    We report the comprehensive clinical characterization of a woman with Fabry disease (FD) carrying a previously unreported truncating\n                    <jats:italic>GLA<\/jats:italic>\n                    variant, c.837_838delinsAT, p.(Gln280Ter). The patient, a 52-year-old woman with longstanding hypertrophic cardiomyopathy, was referred to a specialized Fabry Disease Program to investigate FD as the underlying etiology of her cardiomyopathy. Cardiac magnetic resonance imaging demonstrated diffuse left ventricular hypertrophy with extensive late gadolinium enhancement, indicating advanced replacement fibrosis and an increased arrhythmic risk. Biochemical evaluation revealed reduced\n                    <jats:italic>\u03b1<\/jats:italic>\n                    -galactosidase A activity and markedly elevated Lyso-Gb3 levels. Comprehensive systemic assessment identified bilateral cornea verticillata and nonspecific periventricular white matter hyperintensities on brain magnetic resonance imaging, while renal function remained preserved without clinically significant renal involvement. Molecular analysis identified the heterozygous truncating\n                    <jats:italic>GLA<\/jats:italic>\n                    variant c.837_838delinsAT, p.(Gln280Ter), which had not previously been reported. The patient received an implantable cardioverter-defibrillator following cardiovascular risk assessment and subsequently initiated enzyme replacement therapy with agalsidase beta. This case expands the known mutational spectrum of the\n                    <jats:italic>GLA<\/jats:italic>\n                    gene and illustrates the value of integrating molecular genetic analysis with multimodality cardiac imaging and comprehensive phenotyping in patients with unexplained hypertrophic cardiomyopathy. This integrated approach not only supports the interpretation of previously unreported\n                    <jats:italic>GLA<\/jats:italic>\n                    variants but may also refine etiologic diagnosis, cardiovascular risk assessment, and individualized clinical management in FD.\n                  <\/jats:p>","DOI":"10.3389\/fmed.2026.1970747","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T04:29:26Z","timestamp":1790569766000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Fabry cardiomyopathy associated with a novel truncating GLA variant, c.837_838delinsAT, p.(Gln280Ter)"],"prefix":"10.3389","volume":"13","author":[{"given":"Fernando","family":"Perretta","sequence":"first","affiliation":[{"name":"Department of Nephrology, NEFRA Medical Care","place":["Escobar, Argentina"]},{"name":"Intensive Care Unit, Hospital Zonal General de Agudos Dr. Enrique Erill","place":["Escobar, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Zurita","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hospital Zonal General de Agudos Dr. Enrique Erill","place":["Escobar, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo","family":"Ortiz","sequence":"additional","affiliation":[{"name":"Intensive Care Unit, Hospital Zonal General de Agudos Dr. Enrique Erill","place":["Escobar, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Politei","sequence":"additional","affiliation":[{"name":"Department of Neurology, Fundaci\u00f3n SPINE","place":["CABA, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1016\/j.ymgme.2018.02.014","article-title":"Fabry disease revisited: management and treatment recommendations for adult patients","volume":"123","author":"Ortiz","year":"2018","journal-title":"Mol Genet Metab"},{"key":"B2","volume-title":"ClinVar","year":""},{"key":"B3","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American college of medical genetics and genomics and the association for molecular pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med"},{"key":"B4","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1111\/cge.12613","article-title":"X-chromosome inactivation in female patients with Fabry disease","volume":"89","author":"Echevarria","year":"2016","journal-title":"Clin Genet"},{"key":"B5","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1016\/j.jacc.2020.12.024","article-title":"Cardiac involvement in Fabry disease. JACC review topic of the week","volume":"77","author":"Pieroni","year":"2021","journal-title":"J Am Coll Cardiol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"37","DOI":"10.3390\/genes15010037","article-title":"Fabry disease in women: genetic basis, available biomarkers, and clinical manifestations","volume":"15","author":"Izhar","year":"2023","journal-title":"Genes (Basel)"},{"key":"B7","doi-asserted-by":"publisher","first-page":"544","DOI":"10.6515\/ACS.202409_40(5).20240731A","article-title":"2024 Update of the TSOC expert consensus of Fabry disease","volume":"40","author":"Hung","year":"2024","journal-title":"Acta Cardiol Sin"},{"key":"B8","doi-asserted-by":"publisher","first-page":"4771","DOI":"10.3390\/jcm13164771","article-title":"Contemporary multimodality imaging for diagnosis and management of fabry cardiomyopathy","volume":"13","author":"Kaur","year":"2024","journal-title":"J Clin Med"},{"key":"B9","doi-asserted-by":"publisher","first-page":"i51","DOI":"10.1093\/eurheartjsupp\/suae104","article-title":"Cardiac involvement in Fabry disease: recent advances, unresolved issues, and unmet needs","volume":"27","author":"Pieroni","year":"2025","journal-title":"Eur Heart J Suppl"},{"key":"B10","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1148\/radiol.2019191385","article-title":"Left ventricular hypertrophy and late gadolinium enhancement at cardiac MRI are associated with adverse cardiac events in Fabry disease","volume":"294","author":"Hanneman","year":"2020","journal-title":"Radiology"},{"key":"B11","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1136\/jmedgenet-2019-106467","article-title":"Use of a rare disease registry for establishing phenotypic classification of previously unassigned GLA variants: a consensus classification system by a multispecialty Fabry disease genotype-phenotype workgroup","volume":"57","author":"Germain","year":"2020","journal-title":"J Med Genet"},{"key":"B12","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1093\/ndt\/gfab038","article-title":"Precision medicine in Fabry disease","volume":"36","author":"Lenders","year":"2021","journal-title":"Nephrol Dial Transplant"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1970747\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T04:29:28Z","timestamp":1790569768000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1970747\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,28]]},"references-count":12,"alternative-id":["10.3389\/fmed.2026.1970747"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1970747","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,28]]},"article-number":"1970747"}}