{"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":1791993939562,"version":"4.4.0"},"reference-count":26,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ Cardiovasc Genet"],"published-print":{"date-parts":[[2014,2]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>Currently, no method is available to identify \u03b1-galactosidase A (agalA) mutations determining clinically relevant Fabry disease. In our largest European Fabry cohort, we investigated whether a biomarker, specific for the defect, could stratify persons at risk.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>A total of 124 individuals with agalA mutations were investigated with a comprehensive clinical workup, genetic analysis, and laboratory testing, including measurements of agalA activity and lyso-Gb3 (degradation product of the accumulating Gb3). Additionally, an extensive family screening with a clinical workup of relatives was performed. The patient population was divided into 2 samples: previously described mutations (n=72) and novel mutations (n=52). The patients with previously described mutations were subdivided into 2 groups: classical mutations, which were known to cause the classic type of Fabry disease with specific symptoms and a high risk for major events in all 3 main organs (heart, kidney, and central nervous system), and atypical mutations without the typical presentation. All patients with atypical mutations (n=17) had lower lyso-Gb3 levels than any of the patients with classical Fabry disease (n=55). A cutoff value of 2.7 ng\/mL separated the 2 groups. Six out of 52 patients with novel mutations showed a lyso-Gb3 level &lt;2.7 ng\/mL. Clinical investigation, blinded to lyso-Gb3 results, revealed no classic organ involvement in these patients or their relatives. In contrast, the characterization of patients with lyso-Gb3\u22652.7ng\/mL suggested classical Fabry mutations in most of the patients (93%).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Our data show that the biomarker lyso-Gb3 may identify the clinically relevant agalA mutations leading to Fabry disease.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circgenetics.113.000249","type":"journal-article","created":{"date-parts":[[2014,1,7]],"date-time":"2014-01-07T02:43:10Z","timestamp":1389062590000},"page":"8-16","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":121,"title":["Gene Mutations Versus Clinically Relevant Phenotypes"],"prefix":"10.1161","volume":"7","author":[{"given":"Markus","family":"Niemann","sequence":"first","affiliation":[{"name":"From the Department of Internal Medicine I (M.N., S.S., F.B., G.E., C.W., F.W.), Comprehensive Heart Failure Center (M.N., S.S., F.B., M.B., G.E., C.W., F.W.), Institute of Radiology (M.B.), University of W\u00fcrzburg, W\u00fcrzburg, Germany; The Albrecht-Kossel Institute for Neuroregeneration, University of Rostock, Rostock, Germany (A.R.); and ICREA-Universitat Pompeu Fabra, Barcelona, Spain (B.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arndt","family":"Rolfs","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine I (M.N., S.S., F.B., G.E., C.W., F.W.), Comprehensive Heart Failure Center (M.N., S.S., F.B., M.B., G.E., C.W., F.W.), Institute of Radiology (M.B.), University of W\u00fcrzburg, W\u00fcrzburg, Germany; The Albrecht-Kossel Institute for Neuroregeneration, University of Rostock, Rostock, Germany (A.R.); and ICREA-Universitat Pompeu Fabra, Barcelona, Spain (B.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"St\u00f6rk","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine I (M.N., S.S., F.B., G.E., C.W., F.W.), Comprehensive Heart Failure Center (M.N., S.S., F.B., M.B., G.E., C.W., F.W.), Institute of Radiology (M.B.), University of W\u00fcrzburg, W\u00fcrzburg, Germany; The Albrecht-Kossel Institute for Neuroregeneration, University of Rostock, Rostock, Germany (A.R.); and ICREA-Universitat Pompeu Fabra, Barcelona, Spain (B.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart","family":"Bijnens","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine I (M.N., S.S., F.B., G.E., C.W., F.W.), Comprehensive Heart Failure Center (M.N., S.S., F.B., M.B., G.E., C.W., F.W.), Institute of Radiology (M.B.), University of W\u00fcrzburg, W\u00fcrzburg, Germany; The Albrecht-Kossel Institute for Neuroregeneration, University of Rostock, Rostock, Germany (A.R.); and ICREA-Universitat Pompeu Fabra, Barcelona, Spain (B.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Breunig","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine I (M.N., S.S., F.B., G.E., C.W., F.W.), Comprehensive Heart Failure Center (M.N., S.S., F.B., M.B., G.E., C.W., F.W.), Institute of Radiology (M.B.), University of W\u00fcrzburg, W\u00fcrzburg, Germany; The Albrecht-Kossel Institute for Neuroregeneration, University of Rostock, Rostock, Germany (A.R.); and ICREA-Universitat Pompeu Fabra, Barcelona, Spain (B.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meinrad","family":"Beer","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine I (M.N., S.S., F.B., G.E., C.W., F.W.), Comprehensive Heart Failure Center (M.N., S.S., F.B., M.B., G.E., C.W., F.W.), Institute of Radiology (M.B.), University of W\u00fcrzburg, W\u00fcrzburg, Germany; The Albrecht-Kossel Institute for Neuroregeneration, University of Rostock, Rostock, Germany (A.R.); and ICREA-Universitat Pompeu Fabra, Barcelona, Spain (B.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Ertl","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine I (M.N., S.S., F.B., G.E., C.W., F.W.), Comprehensive Heart Failure Center (M.N., S.S., F.B., M.B., G.E., C.W., F.W.), Institute of Radiology (M.B.), University of W\u00fcrzburg, W\u00fcrzburg, Germany; The Albrecht-Kossel Institute for Neuroregeneration, University of Rostock, Rostock, Germany (A.R.); and ICREA-Universitat Pompeu Fabra, Barcelona, Spain (B.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Wanner","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine I (M.N., S.S., F.B., G.E., C.W., F.W.), Comprehensive Heart Failure Center (M.N., S.S., F.B., M.B., G.E., C.W., F.W.), Institute of Radiology (M.B.), University of W\u00fcrzburg, W\u00fcrzburg, Germany; The Albrecht-Kossel Institute for Neuroregeneration, University of Rostock, Rostock, Germany (A.R.); and ICREA-Universitat Pompeu Fabra, Barcelona, Spain (B.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Weidemann","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine I (M.N., S.S., F.B., G.E., C.W., F.W.), Comprehensive Heart Failure Center (M.N., S.S., F.B., M.B., G.E., C.W., F.W.), Institute of Radiology (M.B.), University of W\u00fcrzburg, W\u00fcrzburg, Germany; The Albrecht-Kossel Institute for Neuroregeneration, University of Rostock, Rostock, Germany (A.R.); and ICREA-Universitat Pompeu Fabra, Barcelona, Spain (B.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2009.072116"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201184"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1096-7192(03)00136-7"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10275"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.108.794529"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehi143"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2009.10.178"},{"key":"e_1_3_4_9_2","first-page":"157","article-title":"Fabry\u2019s disease: enzymatic diagnosis of hemizygotes and heterozygotes. Alpha-galactosidase activities in plasma, serum, urine, and leukocytes.","volume":"81","author":"Desnick RJ","year":"1973","unstructured":"Desnick RJ, Allen KY, Desnick SJ, Raman MK, Bernlohr RW, Krivit W. Fabry\u2019s disease: enzymatic diagnosis of hemizygotes and heterozygotes. Alpha-galactosidase activities in plasma, serum, urine, and leukocytes. J Lab Clin Med. 1973;81:157\u2013171.","journal-title":"J Lab Clin Med"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2010.03227.x"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.13.4859"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/17.8.3301"},{"key":"e_1_3_4_13_2","doi-asserted-by":"crossref","first-page":"21859","DOI":"10.1016\/S0021-9258(18)45818-8","article-title":"Human alpha-N-acetylgalactosaminidase-molecular cloning, nucleotide sequence, and expression of a full-length cDNA: homology with human alpha-galactosidase A suggests evolution from a common ancestral gene.","volume":"265","author":"Wang AM","year":"1990","unstructured":"Wang AM, Bishop DF, Desnick RJ. Human alpha-N-acetylgalactosaminidase-molecular cloning, nucleotide sequence, and expression of a full-length cDNA: homology with human alpha-galactosidase A suggests evolution from a common ancestral gene. J Biol Chem. 1990;265:21859\u201321866.","journal-title":"J Biol Chem"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199102073240607"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1159\/000046124"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jjcc.2007.12.001"},{"key":"e_1_3_4_17_2","first-page":"98","article-title":"End-stage cardiac manifestations and autopsy findings in patients with cardiac fabry disease.","volume":"43","author":"Teraguchi H","year":"2004","unstructured":"Teraguchi H, Takenaka T, Yoshida A, Taguchi S, Ninomiya K, Yoshida H, et al.. End-stage cardiac manifestations and autopsy findings in patients with cardiac fabry disease. J Cardiol. 2004;43:98\u201399.","journal-title":"J Cardiol"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1080\/08035320510031045"},{"key":"e_1_3_4_19_2","volume-title":"Fabry Disease: Perspectives From 5 Years of FOS","author":"Ries M","year":"2006","unstructured":"Ries M, Gal A. Genotype-phenotype correlation in fabry disease. In:, Mehta BM, Sunder-Plassmann G Fabry Disease: Perspectives From 5 Years of FOS. Oxford: Oxford PharmaGenesis;2006."},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-0004.2001.600107.x"},{"key":"e_1_3_4_21_2","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1128\/jcm.27.7.1617-1622.1989","article-title":"Sensitive receptor-specified enzyme-linked immunosorbent assay for Escherichia coli verocytotoxin.","volume":"27","author":"Basta M","year":"1989","unstructured":"Basta M, Karmali M, Lingwood C. Sensitive receptor-specified enzyme-linked immunosorbent assay for Escherichia coli verocytotoxin. J Clin Microbiol. 1989;27:1617\u20131622.","journal-title":"J Clin Microbiol"},{"key":"e_1_3_4_22_2","doi-asserted-by":"crossref","first-page":"2830","DOI":"10.1128\/jcm.28.12.2830-2833.1990","article-title":"Neutralization receptor-based immunoassay for detection of neutralizing antibodies to Escherichia coli verocytotoxin 1.","volume":"28","author":"Boulanger J","year":"1990","unstructured":"Boulanger J, Petric M, Lingwood C, Law H, Roscoe M, Karmali M. Neutralization receptor-based immunoassay for detection of neutralizing antibodies to Escherichia coli verocytotoxin 1. J Clin Microbiol. 1990;28:2830\u20132833.","journal-title":"J Clin Microbiol"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/166.4.832"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0712309105"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2010.03.020"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2010.05.003"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfq080"}],"container-title":["Circulation: Cardiovascular Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCGENETICS.113.000249","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T01:47:02Z","timestamp":1715564822000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCGENETICS.113.000249"}},"subtitle":["Lyso-Gb3 Defines Fabry Disease"],"short-title":[],"issued":{"date-parts":[[2014,2]]},"references-count":26,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2014,2]]}},"alternative-id":["10.1161\/CIRCGENETICS.113.000249"],"URL":"https:\/\/doi.org\/10.1161\/circgenetics.113.000249","relation":{},"ISSN":["1942-325X","1942-3268"],"issn-type":[{"value":"1942-325X","type":"print"},{"value":"1942-3268","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,2]]}}}