{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T04:26:03Z","timestamp":1787199963475,"version":"build-2736575974"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"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. Mol. Biosci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Fabry disease (Anderson\u2013Fabry disease,FD) is an X-linked lysosomal storage disorder caused by variants in GLA, resulting in \u03b1-galactosidase A (\u03b1-Gal A) deficiency and accumulation of globotriaosylsphingosine (lyso-Gb3), with frequent cardiac involvement.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case Summary<\/jats:title>\n                    <jats:p>A 53-year-old man presented with exertional chest tightness and dyspnea. Electrocardiography and echocardiography demonstrated marked left ventricular hypertrophy. Cardiac magnetic resonance revealed diffuse hypertrophy with extensive subendocardial late gadolinium enhancement. ^99mTc-pyrophosphate scintigraphy showed minimal myocardial uptake, arguing against transthyretin cardiac amyloidosis. Biochemical testing showed markedly reduced \u03b1-Gal A activity and elevated lyso-Gb3 levels. Whole-exome sequencing identified a previously unreported GLA variant (NM_000169.3:c.752A&amp;gt;C; p.Glu251Ala), which was confirmed by Sanger sequencing and detected in multiple family members. The variant is currently classified as a variant of uncertain significance (VUS). Familial analysis demonstrated a segregation pattern consistent with X-linked inheritance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We report a novel GLA variant associated with biochemical abnormalities and familial segregation consistent with FD. These findings support a potential role of this variant in Fabry cardiomyopathy and expand the mutational spectrum of GLA, although its pathogenicity requires further validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmolb.2026.1828669","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T04:16:08Z","timestamp":1787199368000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel GLA variant (c.752A&gt;C; p.Glu251Ala) identified in a patient with Fabry cardiomyopathy and familial segregation"],"prefix":"10.3389","volume":"13","author":[{"given":"Ting","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Cardiology, Changde Hospital, Xiangya School of Medicine, Central South University (The First People\u2019s Hospital of Changde City)","place":["Changde, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sulan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Changde Hospital, Xiangya School of Medicine, Central South University (The First People\u2019s Hospital of Changde City)","place":["Changde, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Radiology, Changde Hospital, Xiangya School of Medicine, Central South University (The First People\u2019s Hospital of Changde City)","place":["Changde, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1460","DOI":"10.3390\/biom12101460","article-title":"An overview of molecular mechanisms in FD","volume":"12","author":"Amodio","year":"2022","journal-title":"Biomolecules"},{"key":"B2","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1056\/NEJMoa033349","article-title":"Glycogen storage diseases presenting as hypertrophic cardiomyopathy","volume":"352","author":"Arad","year":"2005","journal-title":"N. 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