{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:05:39Z","timestamp":1791993939500,"version":"4.4.0"},"reference-count":24,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T00:00:00Z","timestamp":1645747200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008769","name":"Julius-Maximilians-Universit\u00e4t W\u00fcrzburg","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Anderson\u2013Fabry disease (FD) is an X\u2010linked lysosomal storage disorder with varying organ involvement and symptoms, depending on the underlying mutation in the alpha\u2010galactosidase A gene (HGNC: <jats:italic>GLA<\/jats:italic>). With genetic testing becoming more readily available, it is crucial to precisely evaluate pathogenicity of each genetic variant, in order to determine whether there is or might be not a need for FD\u2010specific therapy in affected patients and relatives at the time point of presentation or in the future.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This case series investigates the clinical impact of the specific <jats:italic>GLA<\/jats:italic> gene variant <jats:italic>c.376A&gt;G (p.Ser126Gly)<\/jats:italic> in five (one heterozygous and one homozygous female, three males) individuals from different families, who visited our center between 2009 and 2021. Comprehensive neurological, nephrological and cardiac examinations were performed in all cases. One patient received a follow\u2010up examination after 12\u00a0years.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Index events leading to suspicion of FD were mainly unspecific neurological symptoms. However, FD\u2010specific biomarkers, imaging examinations (i.e., brain MRI, heart MRI), and tissue\u2010specific diagnostics, including kidney and skin biopsies, did not reveal evidence for FD\u2010specific symptoms or organ involvement but showed normal results in all cases. This includes findings from 12\u2010year follow\u2010up in one patient with renal biopsy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings suggest that <jats:italic>p.Ser126Gly<\/jats:italic> represents a benign <jats:italic>GLA<\/jats:italic> gene variant which per se does not cause FD. Precise clinical evaluation in individuals diagnosed with genetic variations of unknown significance should be performed to distinguish common symptoms broadly prevalent in the general population from those secondary to FD.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1912","type":"journal-article","created":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T12:50:53Z","timestamp":1645793453000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Gene variants of unknown significance in Fabry disease: Clinical characteristics of <i>c.376A&gt;G (p.Ser126Gly)<\/i>"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4317-8824","authenticated-orcid":false,"given":"Kolja","family":"Lau","sequence":"first","affiliation":[{"name":"Department of Internal Medicine I University Hospital W\u00fcrzburg  W\u00fcrzburg Germany"},{"name":"Fabry Center for Interdisciplinary Therapy (FAZiT) University Hospital W\u00fcrzburg  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurcan","family":"\u00dc\u00e7eyler","sequence":"additional","affiliation":[{"name":"Fabry Center for Interdisciplinary Therapy (FAZiT) University Hospital W\u00fcrzburg  W\u00fcrzburg Germany"},{"name":"Department of Neurology University Hospital W\u00fcrzburg  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tereza","family":"Cairns","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I University Hospital W\u00fcrzburg  W\u00fcrzburg Germany"},{"name":"Fabry Center for Interdisciplinary Therapy (FAZiT) University Hospital W\u00fcrzburg  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lora","family":"Lorenz","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I University Hospital W\u00fcrzburg  W\u00fcrzburg Germany"},{"name":"Fabry Center for Interdisciplinary Therapy (FAZiT) University Hospital W\u00fcrzburg  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Sommer","sequence":"additional","affiliation":[{"name":"Fabry Center for Interdisciplinary Therapy (FAZiT) University Hospital W\u00fcrzburg  W\u00fcrzburg Germany"},{"name":"Department of Neurology University Hospital W\u00fcrzburg  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"Schindeh\u00fctte","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Interventional Neuroradiology University Hospital W\u00fcrzburg  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Amann","sequence":"additional","affiliation":[{"name":"Department of Nephropathology, Department of Pathology University of Erlangen\u2010N\u00fcrnberg  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Wanner","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I University Hospital W\u00fcrzburg  W\u00fcrzburg Germany"},{"name":"Fabry Center for Interdisciplinary Therapy (FAZiT) University Hospital W\u00fcrzburg  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2560-4068","authenticated-orcid":false,"given":"Peter","family":"Nordbeck","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I University Hospital W\u00fcrzburg  W\u00fcrzburg Germany"},{"name":"Fabry Center for Interdisciplinary Therapy (FAZiT) University Hospital W\u00fcrzburg  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,2,25]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005792-200203000-00003"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.110.579409"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/postgradmedj-2018-136056"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2012.10.005"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-5-30"},{"key":"e_1_2_11_7_1","unstructured":"International Fabry Disease Genotype\u2010Phenotype Database (dbFGP.org). 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