{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T13:30:04Z","timestamp":1770903004453,"version":"3.50.1"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ Cardiovasc Genet"],"published-print":{"date-parts":[[2017,8]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>\n              The screening of Icelandic patients clinically diagnosed with hypertrophic cardiomyopathy resulted in identification of 8 individuals from 2 families with X-linked Fabry disease (FD) caused by\n              <jats:italic>GLA<\/jats:italic>\n              (\u03b1-galactosidase A gene) mutations encoding p.D322E (family A) or p.I232T (family B).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>Familial screening of at-risk relatives identified mutations in 16 family A members (8 men and 8 heterozygotes) and 25 family B members (10 men and 15 heterozygotes). Clinical assessments, \u03b1-galactosidase A (\u03b1-GalA) activities, glycosphingolipid substrate levels, and in vitro mutation expression were used to categorize p.D322E as a classic FD mutation and p.I232T as a later-onset FD mutation. In vitro expression revealed that p.D322E and p.I232T had \u03b1-GalA activities of 1.4% and 14.9% of the mean wild-type activity, respectively. Family A men had markedly decreased \u03b1-GalA activity and childhood-onset classic manifestations, except for angiokeratoma and cornea verticillata. Family B men had residual \u03b1-GalA activity and developed FD manifestations in adulthood. Despite these differences, all family A and family B men &gt;30 years of age had left ventricular hypertrophy, which was mainly asymmetrical, and had similar late gadolinium enhancement patterns. Ischemic stroke and severe white matter lesions were more frequent among family A men, but neither family A nor family B men had overt renal disease. Family A and family B heterozygotes had less severe or no clinical manifestations.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>\n              Men with classic or later-onset FD caused by\n              <jats:italic>GLA<\/jats:italic>\n              missense mutations developed prominent and similar cardiovascular disease at similar ages, despite markedly different \u03b1-GalA activities.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circgenetics.116.001639","type":"journal-article","created":{"date-parts":[[2017,8,11]],"date-time":"2017-08-11T01:00:32Z","timestamp":1502413232000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":19,"title":["Fabry Disease in Families With Hypertrophic Cardiomyopathy"],"prefix":"10.1161","volume":"10","author":[{"given":"Berglind","family":"Adalsteinsdottir","sequence":"first","affiliation":[{"name":"From the Faculty of Medicine, University of Iceland, Reykjavik, Iceland (B.A., R.P., R.A., G.T.G.); Division of Cardiology (B.A., R.D.), Department of Genetics (R.A.), Division of Nephrology (R.P.), and Department of Radiology (M.G.), Landspitali\u2013The National University Hospital of Iceland, Reykjavik, Iceland; Department of Cardiology, Haukeland University Hospital, Bergen, Norway (B.A.); Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (R.J.D., B.C...."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Runolfur","family":"Palsson","sequence":"additional","affiliation":[{"name":"From the Faculty of Medicine, University of Iceland, Reykjavik, Iceland (B.A., R.P., R.A., G.T.G.); Division of Cardiology (B.A., R.D.), Department of Genetics (R.A.), Division of Nephrology (R.P.), and Department of Radiology (M.G.), Landspitali\u2013The National University Hospital of Iceland, Reykjavik, Iceland; Department of Cardiology, Haukeland University Hospital, Bergen, Norway (B.A.); Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (R.J.D., B.C...."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert J.","family":"Desnick","sequence":"additional","affiliation":[{"name":"From the Faculty of Medicine, University of Iceland, Reykjavik, Iceland (B.A., R.P., R.A., G.T.G.); Division of Cardiology (B.A., R.D.), Department of Genetics (R.A.), Division of Nephrology (R.P.), and Department of Radiology (M.G.), Landspitali\u2013The National University Hospital of Iceland, Reykjavik, Iceland; Department of Cardiology, Haukeland University Hospital, Bergen, Norway (B.A.); Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (R.J.D., B.C...."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marianna","family":"Gardarsdottir","sequence":"additional","affiliation":[{"name":"From the Faculty of Medicine, University of Iceland, Reykjavik, Iceland (B.A., R.P., R.A., G.T.G.); Division of Cardiology (B.A., R.D.), Department of Genetics (R.A.), Division of Nephrology (R.P.), and Department of Radiology (M.G.), Landspitali\u2013The National University Hospital of Iceland, Reykjavik, Iceland; Department of Cardiology, Haukeland University Hospital, Bergen, Norway (B.A.); Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (R.J.D., B.C...."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Polakit","family":"Teekakirikul","sequence":"additional","affiliation":[{"name":"From the Faculty of Medicine, University of Iceland, Reykjavik, Iceland (B.A., R.P., R.A., G.T.G.); Division of Cardiology (B.A., R.D.), Department of Genetics (R.A.), Division of Nephrology (R.P.), and Department of Radiology (M.G.), Landspitali\u2013The National University Hospital of Iceland, Reykjavik, Iceland; Department of Cardiology, Haukeland University Hospital, Bergen, Norway (B.A.); Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (R.J.D., B.C...."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Maron","sequence":"additional","affiliation":[{"name":"From the Faculty of Medicine, University of Iceland, Reykjavik, Iceland (B.A., R.P., R.A., G.T.G.); Division of Cardiology (B.A., R.D.), Department of Genetics (R.A.), Division of Nephrology (R.P.), and Department of Radiology (M.G.), Landspitali\u2013The National University Hospital of Iceland, Reykjavik, Iceland; Department of Cardiology, Haukeland University Hospital, Bergen, Norway (B.A.); Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (R.J.D., B.C...."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evan","family":"Appelbaum","sequence":"additional","affiliation":[{"name":"From the Faculty of Medicine, University of Iceland, Reykjavik, Iceland (B.A., R.P., R.A., G.T.G.); Division of Cardiology (B.A., R.D.), Department of Genetics (R.A.), Division of Nephrology (R.P.), and Department of Radiology (M.G.), Landspitali\u2013The National University Hospital of Iceland, Reykjavik, Iceland; Department of Cardiology, Haukeland University Hospital, Bergen, Norway (B.A.); Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (R.J.D., B.C...."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulf","family":"Neisius","sequence":"additional","affiliation":[{"name":"From the Faculty of Medicine, University of Iceland, Reykjavik, Iceland (B.A., R.P., R.A., G.T.G.); Division of Cardiology (B.A., R.D.), Department of Genetics (R.A.), Division of Nephrology (R.P.), and Department of Radiology (M.G.), Landspitali\u2013The National University Hospital of Iceland, Reykjavik, Iceland; Department of Cardiology, Haukeland University Hospital, Bergen, Norway (B.A.); Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (R.J.D., B.C...."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barry J.","family":"Maron","sequence":"additional","affiliation":[{"name":"From the Faculty of Medicine, University of Iceland, Reykjavik, Iceland (B.A., R.P., R.A., G.T.G.); Division of Cardiology (B.A., R.D.), Department of Genetics (R.A.), Division of Nephrology (R.P.), and Department of Radiology (M.G.), Landspitali\u2013The National University Hospital of Iceland, Reykjavik, Iceland; Department of Cardiology, Haukeland University Hospital, Bergen, Norway (B.A.); Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (R.J.D., B.C...."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael A.","family":"Burke","sequence":"additional","affiliation":[{"name":"From the Faculty of Medicine, University of Iceland, Reykjavik, Iceland (B.A., R.P., R.A., G.T.G.); Division of Cardiology (B.A., R.D.), Department of Genetics (R.A.), Division of Nephrology (R.P.), and Department of Radiology (M.G.), Landspitali\u2013The National University Hospital of Iceland, Reykjavik, Iceland; Department of Cardiology, Haukeland University Hospital, Bergen, Norway (B.A.); Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (R.J.D., B.C...."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brenden","family":"Chen","sequence":"additional","affiliation":[{"name":"From the Faculty of Medicine, University of Iceland, Reykjavik, Iceland (B.A., R.P., R.A., G.T.G.); Division of Cardiology (B.A., R.D.), Department of Genetics (R.A.), Division of Nephrology (R.P.), and Department of Radiology (M.G.), Landspitali\u2013The National University Hospital of Iceland, Reykjavik, Iceland; Department of Cardiology, Haukeland University Hospital, Bergen, Norway (B.A.); Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (R.J.D., B.C...."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvere","family":"Pagant","sequence":"additional","affiliation":[{"name":"From the Faculty of Medicine, University of Iceland, Reykjavik, Iceland (B.A., R.P., R.A., G.T.G.); Division of Cardiology (B.A., R.D.), Department of Genetics (R.A.), Division of Nephrology (R.P.), and Department of Radiology (M.G.), Landspitali\u2013The National University Hospital of Iceland, Reykjavik, Iceland; Department of Cardiology, Haukeland University Hospital, Bergen, Norway (B.A.); Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (R.J.D., B.C...."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoffer V.","family":"Madsen","sequence":"additional","affiliation":[{"name":"From the Faculty of Medicine, University of Iceland, Reykjavik, Iceland (B.A., R.P., R.A., G.T.G.); Division of Cardiology (B.A., R.D.), Department of Genetics (R.A.), Division of Nephrology (R.P.), and Department of Radiology (M.G.), Landspitali\u2013The National University Hospital of Iceland, Reykjavik, Iceland; Department of Cardiology, Haukeland University Hospital, Bergen, Norway (B.A.); Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (R.J.D., B.C...."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ragnar","family":"Danielsen","sequence":"additional","affiliation":[{"name":"From the Faculty of Medicine, University of Iceland, Reykjavik, Iceland (B.A., R.P., R.A., G.T.G.); Division of Cardiology (B.A., R.D.), Department of Genetics (R.A.), Division of Nephrology (R.P.), and Department of Radiology (M.G.), Landspitali\u2013The National University Hospital of Iceland, Reykjavik, Iceland; Department of Cardiology, Haukeland University Hospital, Bergen, Norway (B.A.); Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (R.J.D., B.C...."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reynir","family":"Arngrimsson","sequence":"additional","affiliation":[{"name":"From the Faculty of Medicine, University of Iceland, Reykjavik, Iceland (B.A., R.P., R.A., G.T.G.); Division of Cardiology (B.A., R.D.), Department of Genetics (R.A.), Division of Nephrology (R.P.), and Department of Radiology (M.G.), Landspitali\u2013The National University Hospital of Iceland, Reykjavik, Iceland; Department of Cardiology, Haukeland University Hospital, Bergen, Norway (B.A.); Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (R.J.D., B.C...."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulla","family":"Feldt-Rasmussen","sequence":"additional","affiliation":[{"name":"From the Faculty of Medicine, University of Iceland, Reykjavik, Iceland (B.A., R.P., R.A., G.T.G.); Division of Cardiology (B.A., R.D.), Department of Genetics (R.A.), Division of Nephrology (R.P.), and Department of Radiology (M.G.), Landspitali\u2013The National University Hospital of Iceland, Reykjavik, Iceland; Department of Cardiology, Haukeland University Hospital, Bergen, Norway (B.A.); Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (R.J.D., B.C...."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan G.","family":"Seidman","sequence":"additional","affiliation":[{"name":"From the Faculty of Medicine, University of Iceland, Reykjavik, Iceland (B.A., R.P., R.A., G.T.G.); Division of Cardiology (B.A., R.D.), Department of Genetics (R.A.), Division of Nephrology (R.P.), and Department of Radiology (M.G.), Landspitali\u2013The National University Hospital of Iceland, Reykjavik, Iceland; Department of Cardiology, Haukeland University Hospital, Bergen, Norway (B.A.); Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (R.J.D., B.C...."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine E.","family":"Seidman","sequence":"additional","affiliation":[{"name":"From the Faculty of Medicine, University of Iceland, Reykjavik, Iceland (B.A., R.P., R.A., G.T.G.); Division of Cardiology (B.A., R.D.), Department of Genetics (R.A.), Division of Nephrology (R.P.), and Department of Radiology (M.G.), Landspitali\u2013The National University Hospital of Iceland, Reykjavik, Iceland; Department of Cardiology, Haukeland University Hospital, Bergen, Norway (B.A.); Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (R.J.D., B.C...."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gunnar Th.","family":"Gunnarsson","sequence":"additional","affiliation":[{"name":"From the Faculty of Medicine, University of Iceland, Reykjavik, Iceland (B.A., R.P., R.A., G.T.G.); Division of Cardiology (B.A., R.D.), Department of Genetics (R.A.), Division of Nephrology (R.P.), and Department of Radiology (M.G.), Landspitali\u2013The National University Hospital of Iceland, Reykjavik, Iceland; Department of Cardiology, Haukeland University Hospital, Bergen, Norway (B.A.); Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (R.J.D., B.C...."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","volume-title":"In: The Online Metabolic and Molecular Bases of Inherited Diseases (OMMBID)","author":"Desnick RJ","year":"2014","unstructured":"Desnick RJ, Ioannou YA, Eng CM. \u03b1-Galactosidase A Deficiency: Fabry Disease. , Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, , et al., eds. In: The Online Metabolic and Molecular Bases of Inherited Diseases (OMMBID). New York, NY: McGraw-Hill; 2014. http:\/\/ommbid.mhmedical.com\/content.aspx?bookid=971&Sectionid=62644837 Accessed August 26, 2016."},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-5-30"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199102073240607"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2014.10.003"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199508033330504"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfq073"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2007.06.062"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2011-300364"},{"key":"e_1_3_4_10_2","first-page":"67","article-title":"Angiokeratoma corporis diffusum\u2013Fabry\u2019s disease.","volume":"34","author":"Colombi A","year":"1967","unstructured":"Colombi A, Kostyal A, Bracher R, Gloor F, Mazzi R, Th\u00f6len H. 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