{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T18:35:31Z","timestamp":1777660531750,"version":"3.51.4"},"reference-count":48,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Genetic Testing and Molecular Biomarkers"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>Osteogenesis imperfecta (OI) includes a group of disorders characterized by susceptibility to bone fractures with different severities. The increasing number of genes that may underlie the disorder, along with the broad phenotypic spectrum that overlaps with other skeletal diseases, provided a compelling case for the use of high-throughput sequencing (HTS) technology as an aid to OI diagnoses. The aim of this analysis was to present the data from our 5-year targeted HTS results, that includes the reporting of 9 novel and 24 known mutations, found in OI patients, from 5 different regions of Turkey.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods:<\/jats:title>\n                    <jats:p>\n                      We performed a retrospective cross-sectional study, reporting the HTS results of 43 patients (23 female and 20 male; mean age: 9.5 years), directed to our center with a suspicion of OI between February 2015 and May 2020. Genetic analyses were also performed for 24 asymptomatic parents to aid the segregation analyses. We utilized an HTS panel targeting the coding regions of 57 genes associated with a reduction, increase, or abnormal development of bone mineralization. In addition, we sequenced the entire coding region of the\n                      <jats:italic toggle=\"yes\">IFITM5<\/jats:italic>\n                      gene through HTS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Thirty-nine patients had at least one pathogenic\/likely pathogenic variation (90.69%) in the\n                      <jats:italic toggle=\"yes\">COL1A1<\/jats:italic>\n                      (56.41%),\n                      <jats:italic toggle=\"yes\">COL1A2<\/jats:italic>\n                      (20.51%),\n                      <jats:italic toggle=\"yes\">FKBP10<\/jats:italic>\n                      (7.7%),\n                      <jats:italic toggle=\"yes\">P3H1<\/jats:italic>\n                      (5.13%),\n                      <jats:italic toggle=\"yes\">IFITM<\/jats:italic>\n                      5 (5.13%),\n                      <jats:italic toggle=\"yes\">CTRAP<\/jats:italic>\n                      (2.56%), or\n                      <jats:italic toggle=\"yes\">TMEM38B<\/jats:italic>\n                      (2.56%) genes. Nine of the determined pathogenic\/likely pathogenic variations were novel. The recurrent pathogenic mutations were c.1081C&gt;T (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/p.Arg361Ter\">p.Arg361Ter<\/jats:ext-link>\n                      ) (3\/43), c.1405C&gt;T (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/p.Arg469Ter\">p.Arg469Ter<\/jats:ext-link>\n                      ) (2\/43), and c.3749del (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/p.Gly1250AlafsTer81\">p.Gly1250AlafsTer81<\/jats:ext-link>\n                      ) in\n                      <jats:italic toggle=\"yes\">COL1A1<\/jats:italic>\n                      gene, along with c.-14C&gt;T variation in the 5\u2019UTR of the\n                      <jats:italic toggle=\"yes\">IFITM5<\/jats:italic>\n                      gene (2\/43) and the c.890_897dup variation in the\n                      <jats:italic toggle=\"yes\">FKBP10<\/jats:italic>\n                      gene (2\/43). Three out of 43 patients were carrying at least one additional variant of unknown significance, highlighting the importance of a multigene panel approach and segregation analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>We suggest that a targeted HTS panel is a feasible tool for genetic diagnosis of OI in patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/gtmb.2020.0169","type":"journal-article","created":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T09:02:18Z","timestamp":1611133338000},"page":"59-67","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["Targeted High-Throughput Sequencing Analysis Results of Osteogenesis Imperfecta Patients from Different Regions of Turkey"],"prefix":"10.1177","volume":"25","author":[{"given":"Selma","family":"Demir","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Trakya University Faculty of Medicine, Edirne, Turkey."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sinem","family":"Yal\u00e7\u0131ntepe","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Trakya University Faculty of Medicine, Edirne, Turkey."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emine \u0130kbal","family":"Atl\u0131","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Trakya University Faculty of Medicine, Edirne, Turkey."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asl\u0131han","family":"Sanr\u0131","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Samsun Ondokuz May\u0131s \u00dcniversitesi, Samsun, Turkey."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruken","family":"Y\u0131ld\u0131r\u0131m","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, Diyarbak\u0131r Hospital of Pediatric Diseases, Diyarbak\u0131r, Turkey."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Filiz","family":"T\u00fct\u00fcnc\u00fcler","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology and Trakya University Faculty of Medicine, Edirne, Turkey."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mehmet","family":"\u00c7elik","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Trakya University Faculty of Medicine, Edirne, Turkey."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Engin","family":"Atl\u0131","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Trakya University Faculty of Medicine, Edirne, Turkey."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u015eebnem","family":"\u00d6zemri Sa\u011f","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine, Uluda\u011f University, Bursa, Turkey."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Damla","family":"Eker","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Trakya University Faculty of Medicine, Edirne, Turkey."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sehime","family":"Temel","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine, Uluda\u011f University, Bursa, Turkey."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hakan","family":"G\u00fcrkan","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Trakya University Faculty of Medicine, Edirne, Turkey."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2021,1,18]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"crossref","unstructured":"Adzhubei I Jordan DM Sunyaev SR (2013) Predicting functional effect of human missense mutations using PolyPhen-2. 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