{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T19:28:55Z","timestamp":1789586935422,"version":"build-2803163510"},"reference-count":16,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Anderson Fabry disease (AFD) is an X-linked hereditary lysosomal abnormality that causes the accumulation of glycosphingolipids in body fluids and tissues, leading to progressive organ damage and a shortened life span. More than 1000 mutations in the GLA gene have been identified, promoting many different clinical pictures. For this reason, diagnosing AFD can be difficult, especially because of the great diversity of atypical clinical presentations that can simulate the disease. Some of these variants of the GLA gene have been described as non-pathogenic. For example, the D313Y variant is one of the most controversial, even if there are several case reports of D313Y patients presenting with signs and symptoms consistent with AFD without any other etiological explanation. This work aimed to clarify whether the presence of the D313Y variant affects \u03b1-Gal A activity and causes AFD symptoms and organ involvement in two patients from different families. The presence of the D313Y variant resulted in clinical manifestations of AFD in both patients and a decrease in alpha-galactosidase activity in the male patient. Two patients (one female and one male) from two unrelated families were examined. Sequencing of all seven GLA exons and the adjacent 5\u2032 and 3\u2032 exon\u2013intron boundaries identified the D313Y variant in exon 6, as well as the genetic variation g.1170C&gt;T in the flanking 5\u2032 UTR in patient 1 only. Our results suggest that the D313Y variant is causative for the disease and that the clinical phenotype can be enhanced by the presence of other variants modulating protein expression.<\/jats:p>","DOI":"10.3390\/ijms26094400","type":"journal-article","created":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T05:54:43Z","timestamp":1746510883000},"page":"4400","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Potential Pathogenetic Role of the D313Y Mutation in the GLA Gene in Anderson Fabry Disease: Two Case Reports"],"prefix":"10.3390","volume":"26","author":[{"given":"Antonella","family":"La Russa","sequence":"first","affiliation":[{"name":"Nephrology Unit, Department of Health Sciences, \u201cMagna Graecia\u201d University, I-88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5360-9926","authenticated-orcid":false,"given":"Antonio","family":"Siniscalchi","sequence":"additional","affiliation":[{"name":"Department of Neurology and Stroke Unit, Annunziata Hospital, I-87100 Cosenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ardito","family":"Bonaventura","sequence":"additional","affiliation":[{"name":"Department of Neurology and Stroke Unit, Della Murgia Fabio Perinei Hospital, I-70022 Altamura, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Di Noia","sequence":"additional","affiliation":[{"name":"Department of Neurology and Stroke Unit, Della Murgia Fabio Perinei Hospital, I-70022 Altamura, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Valsania","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Dialysis, ASL \u201cGuglielmo da Saliceto\u201d Hospital Piacenza, I-29121 Piacenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Stallone","sequence":"additional","affiliation":[{"name":"Nephrology Dialysis and Transplantation Unit, Advance Research Center on Kidney Aging (A.R.cK.A.), Department of Medical and Surgical Sciences, University of Foggia, I-71100 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciano","family":"Tartaglia","sequence":"additional","affiliation":[{"name":"Nephrology Dialysis and Transplantation Unit, Advance Research Center on Kidney Aging (A.R.cK.A.), Department of Medical and Surgical Sciences, University of Foggia, I-71100 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Concetta","family":"Chiapparino","sequence":"additional","affiliation":[{"name":"Department of Neurology and Stroke Unit, Della Murgia Fabio Perinei Hospital, I-70022 Altamura, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Di Rienzo","sequence":"additional","affiliation":[{"name":"U.O.S.V.D. Patologia Clinica, Ospedale Della Murgia Fabio Perinei, I-70022 Altamura, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8000-0681","authenticated-orcid":false,"given":"Giuseppe","family":"Coppolino","sequence":"additional","affiliation":[{"name":"Nephrology Unit, Department of Health Sciences, \u201cMagna Graecia\u201d University, I-88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3032-245X","authenticated-orcid":false,"given":"Davide","family":"Bolignano","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, \u201cMagna Graecia\u201d University, I-88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Faga","sequence":"additional","affiliation":[{"name":"Renal Unit, Campus \u201cS. Venuta\u201d, \u201cRenato Dulbecco\u201d University Hospital, I-88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashour","family":"Michael","sequence":"additional","affiliation":[{"name":"Nephrology Unit, Department of Health Sciences, \u201cMagna Graecia\u201d University, I-88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9563-2216","authenticated-orcid":false,"given":"Alberto","family":"Montesanto","sequence":"additional","affiliation":[{"name":"Department of Biology, Ecology and Earth Sciences, University of Calabria, I-87036 Rende, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4477-7412","authenticated-orcid":false,"given":"Raffaele","family":"Serra","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, \u201cMagna Graecia\u201d University, I-88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7974-3792","authenticated-orcid":false,"given":"Michele","family":"Andreucci","sequence":"additional","affiliation":[{"name":"Nephrology Unit, Department of Health Sciences, \u201cMagna Graecia\u201d University, I-88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.ymgme.2022.07.010","article-title":"An Expert Consensus on Practical Clinical Recommendations and Guidance for Patients with Classic Fabry Disease","volume":"137","author":"Germain","year":"2022","journal-title":"Mol. 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