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dc.contributor.authorAdalsteinsdottir, Berglind
dc.contributor.authorPalsson, Runolfur
dc.contributor.authorDesnick, Robert J
dc.contributor.authorGardarsdottir, Marianna
dc.contributor.authorTeekakirikul, Polakit
dc.contributor.authorMaron, Martin
dc.contributor.authorAppelbaum, Evan
dc.contributor.authorNeisius, Ulf
dc.contributor.authorMaron, Barry J
dc.contributor.authorBurke, Michael A
dc.contributor.authorChen, Brenden
dc.contributor.authorPagant, Silvere
dc.contributor.authorMadsen, Christoffer V
dc.contributor.authorDanielsen, Ragnar
dc.contributor.authorArngrimsson, Reynir
dc.contributor.authorFeldt-Rasmussen, Ulla
dc.contributor.authorSeidman, Jonathan G
dc.contributor.authorSeidman, Christine E
dc.contributor.authorGunnarsson, Gunnar Th
dc.date.accessioned2017-09-20T13:26:11Z
dc.date.available2017-09-20T13:26:11Z
dc.date.issued2017-08
dc.date.submitted2017
dc.identifier.citationFabry Disease in Families With Hypertrophic Cardiomyopathy: Clinical Manifestations in the Classic and Later-Onset Phenotypes. 2017, 10 (4) Circ Cardiovasc Geneten
dc.identifier.issn1942-3268
dc.identifier.pmid28798024
dc.identifier.doi10.1161/CIRCGENETICS.116.001639
dc.identifier.urihttp://hdl.handle.net/2336/620297
dc.descriptionTo access publisher's full text version of this article click on the hyperlink belowen
dc.description.abstractThe 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 GLA(α-galactosidase A gene) mutations encoding p.D322E (family A) or p.I232T (family B).
dc.description.abstractFamilial 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, α-galactosidase A (α-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 α-GalA activities of 1.4% and 14.9% of the mean wild-type activity, respectively. Family A men had markedly decreased α-GalA activity and childhood-onset classic manifestations, except for angiokeratoma and cornea verticillata. Family B men had residual α-GalA activity and developed FD manifestations in adulthood. Despite these differences, all family A and family B men >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.
dc.description.abstractMen with classic or later-onset FD caused by GLA missense mutations developed prominent and similar cardiovascular disease at similar ages, despite markedly different α-GalA activities.
dc.description.sponsorshipAkureyri Hospital Research Fund Landspitali-The National University Hospital of Iceland Research Fund Howard Hughes Medical Institute National Institute of Health Novo Nordic Foundationen
dc.language.isoenen
dc.publisherLippincott Williams & Wilkinsen
dc.relation.urlhttp://ovidsp.uk.ovid.com/sp-3.26.1a/ovidweb.cgi?WebLinkFrameset=1&S=KJBPPDDJFLHFNDFEFNGKGGJHFFMNAA00&returnUrl=ovidweb.cgi%3f%26Full%2bText%3dL%257cS.sh.22.23%257c0%257c01337497-201708000-00008%26S%3dKJBPPDDJFLHFNDFEFNGKGGJHFFMNAA00&directlink=http%3a%2f%2fovidsp.uk.ovid.com%2fovftpdfs%2fPDHFFNJHGGFEFL00%2ffs047%2fovft%2flive%2fgv024%2f01337497%2f01337497-201708000-00008.pdf&filename=Fabry+Disease+in+Families+With+Hypertrophic+Cardiomyopathy%3a+Clinical+Manifestations+in+the+Classic+and+Later-Onset+Phenotypes.&pdf_key=PDHFFNJHGGFEFL00&pdf_index=/fs047/ovft/live/gv024/01337497/01337497-201708000-00008en
dc.rightsArchived with thanks to Circulation. Cardiovascular geneticsen
dc.subjectEfnaskiptasjúkdómaren
dc.subjectHjartasjúklingaren
dc.subjectCAR12en
dc.subjectMAB12en
dc.subjectNEP12en
dc.subjectDAI12en
dc.subject.meshFabry Diseaseen
dc.subject.meshCardiomyopathy, Hypertrophicen
dc.subject.meshIcelanden
dc.titleFabry Disease in Families With Hypertrophic Cardiomyopathy: Clinical Manifestations in the Classic and Later-Onset Phenotypes.en
dc.typeArticleen
dc.contributor.department[ 1 ] Univ Iceland, Fac Med, Reykjavik, Iceland [ 2 ] Landspitali Natl Univ Hosp Iceland, Div Cardiol, Reykjavik, Iceland [ 3 ] Landspitali Natl Univ Hosp Iceland, Dept Genet, Reykjavik, Iceland [ 4 ] Landspitali Natl Univ Hosp Iceland, Div Nephrol, Reykjavik, Iceland [ 5 ] Landspitali Natl Univ Hosp Iceland, Dept Radiol, Reykjavik, Iceland Show the Organization-Enhanced name(s) [ 6 ] Haukeland Hosp, Dept Cardiol, Bergen, Norway Show the Organization-Enhanced name(s) [ 7 ] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA Show the Organization-Enhanced name(s) [ 8 ] Harvard Med Sch, Dept Genet, Boston, MA USA Show the Organization-Enhanced name(s) [ 9 ] Beth Israel Deaconess Med Ctr, Div Cardiovasc Med, Boston, MA 02215 USA [ 10 ] Tufts Med Ctr, Hypertroph Cardiomyopathy Ctr, Div Cardiol, Boston, MA USA Show the Organization-Enhanced name(s) [ 11 ] Brigham & Womens Hosp, Cardiovasc Div, Boston, MA 02115 USA Show the Organization-Enhanced name(s) [ 12 ] Emory Univ, Sch Med, Div Cardiol, Atlanta, GA 30322 USA Show the Organization-Enhanced name(s) [ 13 ] Rigshosp, Dept Med Endocrinol, Copenhagen, Denmark Show the Organization-Enhanced name(s) [ 14 ] Univ Copenhagen, Copenhagen, Denmark Show the Organization-Enhanced name(s) [ 15 ] Howard Hughes Med Inst, Boston, MA 02115 USA [ 16 ] Akureyri Hosp, Dept Med, Akureyri, Icelanden
dc.identifier.journalCirculation. Cardiovascular geneticsen
dc.rights.accessLandspitali Access - LSH-aðganguren
html.description.abstractThe 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 GLA(α-galactosidase A gene) mutations encoding p.D322E (family A) or p.I232T (family B).
html.description.abstractFamilial 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, α-galactosidase A (α-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 α-GalA activities of 1.4% and 14.9% of the mean wild-type activity, respectively. Family A men had markedly decreased α-GalA activity and childhood-onset classic manifestations, except for angiokeratoma and cornea verticillata. Family B men had residual α-GalA activity and developed FD manifestations in adulthood. Despite these differences, all family A and family B men >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.
html.description.abstractMen with classic or later-onset FD caused by GLA missense mutations developed prominent and similar cardiovascular disease at similar ages, despite markedly different α-GalA activities.


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