{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:14:46Z","timestamp":1790799286846,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,2,20]],"date-time":"2013-02-20T00:00:00Z","timestamp":1361318400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Duchenne muscular dystrophy (DMD) displays a clinical range that is not fully explained by the primary\n                      <jats:italic>DMD<\/jats:italic>\n                      mutations.\n                      <jats:italic>Ltbp4<\/jats:italic>\n                      , encoding latent transforming growth factor\u2010\u03b2 binding protein 4, was previously discovered in a genome\u2010wide scan as a modifier of murine muscular dystrophy. We sought to determine whether\n                      <jats:italic>LTBP4<\/jats:italic>\n                      genotype influenced DMD severity in a large patient cohort.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We analyzed nonsynonymous single nucleotide polymorphisms (SNPs) from human\n                      <jats:italic>LTBP4<\/jats:italic>\n                      in 254 nonambulatory subjects with known\n                      <jats:italic>DMD<\/jats:italic>\n                      mutations. These SNPs, V194I, T787A, T820A, and T1140M, form the VTTT and IAAM\n                      <jats:italic>LTBP4<\/jats:italic>\n                      haplotypes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Individuals homozygous for the IAAM\n                      <jats:italic>LTBP4<\/jats:italic>\n                      haplotype remained ambulatory significantly longer than those heterozygous or homozygous for the VTTT haplotype. Glucocorticoid\u2010treated patients who were IAAM homozygotes lost ambulation at 12.5 \u00b1 3.3 years compared to 10.7 \u00b1 2.1 years for treated VTTT heterozygotes or homozygotes. IAAM fibroblasts exposed to transforming growth factor (TGF) \u03b2 displayed reduced phospho\u2010SMAD signaling compared to VTTT fibroblasts, consistent with LTBP4' role as a regulator of TGF\u03b2.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>\n                      <jats:italic>LTBP4<\/jats:italic>\n                      haplotype influences age at loss of ambulation, and should be considered in the management of DMD patients. ANN NEUROL 2013;73:481\u2013488\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.23819","type":"journal-article","created":{"date-parts":[[2012,11,26]],"date-time":"2012-11-26T13:49:39Z","timestamp":1353937779000},"page":"481-488","source":"Crossref","is-referenced-by-count":219,"title":["<i>\n                      <scp>LTBP4<\/scp>\n                    <\/i>\n                    genotype predicts age of ambulatory loss in duchenne muscular dystrophy"],"prefix":"10.1002","volume":"73","author":[{"given":"Kevin M.","family":"Flanigan","sequence":"first","affiliation":[{"name":"Center for Gene Therapy Nationwide Children' Hospital Columbus OH"},{"name":"Department of Pediatrics Ohio State University Columbus OH"},{"name":"Department of Neurology Ohio State University Columbus OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ermelinda","family":"Ceco","sequence":"additional","affiliation":[{"name":"Department of Medicine Department of Human Genetics Committee on Cell Physiology University of Chicago Chicago IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kay\u2010Marie","family":"Lamar","sequence":"additional","affiliation":[{"name":"Department of Medicine Department of Human Genetics Committee on Cell Physiology University of Chicago Chicago IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuuki","family":"Kaminoh","sequence":"additional","affiliation":[{"name":"Center for Gene Therapy Nationwide Children' Hospital Columbus OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane M.","family":"Dunn","sequence":"additional","affiliation":[{"name":"Department of Human Genetics University of Utah School of Medicine Salt Lake City UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerry R.","family":"Mendell","sequence":"additional","affiliation":[{"name":"Center for Gene Therapy Nationwide Children' Hospital Columbus OH"},{"name":"Department of 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