{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T02:01:56Z","timestamp":1779328916240,"version":"3.51.4"},"reference-count":0,"publisher":"S. Karger AG","issue":"3","license":[{"start":{"date-parts":[[2019,10,30]],"date-time":"2019-10-30T00:00:00Z","timestamp":1572393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2019,10,30]],"date-time":"2019-10-30T00:00:00Z","timestamp":1572393600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nephron"],"published-print":{"date-parts":[[2020]]},"abstract":"<b><i>Background:<\/i><\/b> Fabry disease (FD) is a rare X-linked storage disorder resulting from the deficient activity of the lysosomal hydrolase \u03b1-galactosidase A (\u03b1-Gal A). Here we describe a 23-year-old man with FD possessing a novel mutation in the <i>GLA<\/i> gene, the evaluation of his family, and the functional characterization of the novel variant. <b><i>Methods:<\/i><\/b> Two generations of a family were screened for FD by clinical symptoms and low enzymatic activity. This step was followed by DNA sequencing that showed a novel <i>GLA<\/i> missense mutation. To confirm the pathogenicity potential of the mutation, we employed site-directed polymerase chain reaction mutagenesis. <i>GLA<\/i> wild-type and mutant plasmids were transfected into mammalian cells; RNA and proteins were extracted for expression and analysis of enzymatic activity. <b><i>Results:<\/i><\/b> The patient presents the variant p.Asn34Asp in the <i>GLA<\/i> and had several manifestations of FD since adolescence. The investigation of the deficiency of \u03b1-Gal A was initiated due to stage 4 of chronic kidney disease. All family members carrying the novel mutation presented early symptoms, including index case\u2019s mother, who received a renal transplant when she was 35 years old. <i>In silico<\/i> and in vitro analysis confirmed the pathogenic potential of the mutation p.Asn34Asp showing that the enzyme had only 4% of residual activity due to protein misfolding. The ability of the pharmacological chaperone 1-deoxygalactonojirimycin to recover the mutant was confirmed, producing 37.5% of residual activity. <b><i>Conclusion:<\/i><\/b> In this work, we present a novel missense mutation in <i>GLA<\/i> that leads to the production of a catalytically competent \u03b1-Gal A, which is degraded before its delivery to the lysosome, promoting severe manifestations of FD, with a very similar disease course in affected men and women.<\/jats:p>","DOI":"10.1159\/000503998","type":"journal-article","created":{"date-parts":[[2019,10,30]],"date-time":"2019-10-30T22:00:39Z","timestamp":1572472839000},"page":"147-155","source":"Crossref","is-referenced-by-count":10,"title":["Functional Characterization and Pharmacological Evaluation of a Novel <b><i>GLA<\/i><\/b> Missense Mutation Found in a Severely Affected Fabry Disease Family"],"prefix":"10.1159","volume":"144","author":[{"given":"Patr\u00edcia","family":"Varela","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianna","family":"Mastroianni\u00a0Kirsztajn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henrique","family":"Ferrer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina","family":"Aranda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krissia","family":"Wallbach","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gustavo","family":"Ferreira\u00a0da\u00a0Mata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luiz\u00a0A.","family":"Moura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u00edlvia\u00a0R.","family":"Moreira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"Mendes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco\u00a0A.","family":"Curiati","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana\u00a0Maria","family":"Martins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4507-632X","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Bosco\u00a0Pesquero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2019,10,30]]},"container-title":["Nephron"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/503998","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/503998","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T16:06:39Z","timestamp":1745424399000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000503998"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,30]]},"references-count":0,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,2,26]]},"published-print":{"date-parts":[[2020,2,26]]}},"URL":"https:\/\/doi.org\/10.1159\/000503998","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.10078922","asserted-by":"subject"}]},"ISSN":["1660-8151","2235-3186"],"issn-type":[{"value":"1660-8151","type":"print"},{"value":"2235-3186","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,30]]}}}