{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T15:23:04Z","timestamp":1784992984559,"version":"3.55.0"},"reference-count":40,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,3,12]],"date-time":"2018-03-12T00:00:00Z","timestamp":1520812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Multiple osteochondromas is a dysplasia characterized by growth of two or more osteochondromas. It is genetically heterogeneous, caused by pathogenic variants in <jats:italic><jats:styled-content style=\"fixed-case\">EXT<\/jats:styled-content>1<\/jats:italic> or <jats:italic><jats:styled-content style=\"fixed-case\">EXT<\/jats:styled-content>2<\/jats:italic> genes in 70%\u201390% of patients. The <jats:italic><jats:styled-content style=\"fixed-case\">EXT<\/jats:styled-content>1<\/jats:italic> is more often mutated than <jats:italic><jats:styled-content style=\"fixed-case\">EXT<\/jats:styled-content>2<\/jats:italic> gene, with a variable prevalence between populations. There are no data about <jats:italic><jats:styled-content style=\"fixed-case\">EXT<\/jats:styled-content>1<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">EXT<\/jats:styled-content>2<\/jats:italic> pathogenic variants in patients with multiple osteochondromas in Brazilian population. The aim of this survey is to characterize these to determine the genotype profile of this population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> sequencing (Sanger Method) and <jats:styled-content style=\"fixed-case\">MLPA<\/jats:styled-content> analysis were performed to identify point mutations and deletions\/duplications in the sample of 153 patients in 114 families.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Germline variants were identified in 83% of families in which <jats:italic><jats:styled-content style=\"fixed-case\">EXT<\/jats:styled-content>2<\/jats:italic> variants were detected in 46% and <jats:italic><jats:styled-content style=\"fixed-case\">EXT<\/jats:styled-content>1<\/jats:italic> in 37% of cases. No variants were detected in 17% of them. We identified 50 different variants, 33 (13 frameshift, 11 nonsense, 5 missense, 2 splice site mutation, and 2 large deletions) in <jats:italic><jats:styled-content style=\"fixed-case\">EXT<\/jats:styled-content>1<\/jats:italic> and 17 (6 frameshift, 6 splice site mutation, 3 nonsense, 1 missense, and 1 large deletion) in <jats:italic><jats:styled-content style=\"fixed-case\">EXT<\/jats:styled-content>2<\/jats:italic>. Of all 50 variants, 31 (62%) were novel, including 20 out of 33 (60,6%) <jats:italic><jats:styled-content style=\"fixed-case\">EXT<\/jats:styled-content>1<\/jats:italic> and 11 out of 17 (64.7%) <jats:italic><jats:styled-content style=\"fixed-case\">EXT<\/jats:styled-content>2<\/jats:italic> alleles. The vast majority of variants (88%) were \u201closs\u2010of\u2010function\u201d and two novel hotspots in <jats:italic><jats:styled-content style=\"fixed-case\">EXT<\/jats:styled-content>2<\/jats:italic> gene were observed in our study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The prevalence of variants detected in the <jats:italic><jats:styled-content style=\"fixed-case\">EXT<\/jats:styled-content>2<\/jats:italic> gene differs from other researches from Latin America, European, and Asian population. This uncommon prevalence could be related with the newly characterized variant hotspot sites detected in <jats:italic><jats:styled-content style=\"fixed-case\">EXT<\/jats:styled-content>2<\/jats:italic> gene (p.Ala409Profs*26 and p.Ser290*). A high number of novel variants were also identified indicating that Brazilian population has a unique genetic profile. Characterizing this population and establishing its genotype is essential to understand the molecular pathogenesis of this disease in Brazil.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.382","type":"journal-article","created":{"date-parts":[[2018,3,15]],"date-time":"2018-03-15T10:09:06Z","timestamp":1521108546000},"page":"382-392","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Analysis of mutations in <i><scp>EXT<\/scp>1<\/i> and <i><scp>EXT<\/scp>2<\/i> in Brazilian patients with multiple osteochondromas"],"prefix":"10.1002","volume":"6","author":[{"given":"Savana C. L.","family":"Santos","sequence":"first","affiliation":[{"name":"Molecular Pathology Laboratory SARAH Network of Rehabilitation Hospitals Bras\u00edlia Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8339-6837","authenticated-orcid":false,"given":"Isabela M. P. O.","family":"Rizzo","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics SARAH Network of Rehabilitation Hospitals Bras\u00edlia Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinaldo I.","family":"Takata","sequence":"additional","affiliation":[{"name":"Molecular Pathology Laboratory SARAH Network of Rehabilitation Hospitals Bras\u00edlia Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos E.","family":"Speck\u2010Martins","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics SARAH Network of Rehabilitation Hospitals Bras\u00edlia Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime M.","family":"Brum","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics SARAH Network of Rehabilitation Hospitals Bras\u00edlia Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Sollaci","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics SARAH Network of Rehabilitation Hospitals Bras\u00edlia Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,3,12]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1095-137"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2006.00653.x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1086\/303004"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-3-3"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2012.11.055"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep06407"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.38.7.430"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0215(20011120)95:6<378::AID-IJC1067>3.0.CO;2-F"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11596-014-1230-3"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.10635"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.2127"},{"key":"e_1_2_6_13_1","first-page":"80","article-title":"Hereditary multiple exostoses (EXT): Mutational studies of familial EXT1 cases and EXT\u2010associated malignancies","volume":"60","author":"Hecht J. 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