{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T07:06:24Z","timestamp":1775804784226,"version":"3.50.1"},"reference-count":57,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:00:00Z","timestamp":1760486400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:00:00Z","timestamp":1760486400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Osteogenesis imperfecta (OI) is a genetically heterogeneous connective tissue disorder marked by bone fragility and deformities. This study aimed to define the clinical and molecular characteristics of 21 OI patients from 15 unrelated Egyptian families. Most probands were analyzed by exome sequencing. In three consanguineous cases, variants were identified through SNP array\u2010based homozygosity mapping followed by direct sequencing of a candidate gene. Genotype\u2013phenotype correlations were additionally explored. Parental consanguinity was documented in 66.7% (10\/15) of the total cohort and in 100% (8\/8) of the families with autosomal recessive OI. Pathogenic or likely pathogenic variants were identified in 14 families, five of which were novel. A variant of uncertain significance was identified in the remaining family.\n                    <jats:italic>COL1A1<\/jats:italic>\n                    and\n                    <jats:italic>COL1A2<\/jats:italic>\n                    (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20097) were the most commonly mutated genes, followed by\n                    <jats:italic>CRTAP<\/jats:italic>\n                    (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20094), while variants in\n                    <jats:italic>P3H1<\/jats:italic>\n                    ,\n                    <jats:italic>WNT1<\/jats:italic>\n                    ,\n                    <jats:italic>CREB3L1<\/jats:italic>\n                    , and\n                    <jats:italic>SEC24D<\/jats:italic>\n                    were each identified in a single patient. The present study highlights the molecular heterogeneity of OI. In total, 15 distinct variants in seven OI\u2010related genes were identified. We also report a particularly high number of OI lethal forms affecting 10 patients out of 21. The study adds further evidence for the utility of ES in the genetic diagnosis of OI, which facilitates counseling and personalized care.\n                  <\/jats:p>","DOI":"10.1111\/cge.70091","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T19:39:35Z","timestamp":1760557175000},"page":"665-678","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic and Clinical Spectrum of Osteogenesis Imperfecta in an Egyptian Cohort With a High Rate of Lethal Phenotypes"],"prefix":"10.1111","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8510-8050","authenticated-orcid":false,"given":"Ghada","family":"Elhady","sequence":"first","affiliation":[{"name":"Department of Human Genetics, Medical Research Institute Alexandria University  Alexandria Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asmaa K.","family":"Amin","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Medical Research Institute Alexandria University  Alexandria Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7896-8519","authenticated-orcid":false,"given":"Asier","family":"Iturrate","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas Sols\u2010Morreale Consejo Superior de Investigaciones Cient\u00edficas\u2010Universidad Aut\u00f3noma de Madrid  Madrid Spain"},{"name":"CIBERER\u2010Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7572-9128","authenticated-orcid":false,"given":"Sara","family":"El\u2010Dessouky","sequence":"additional","affiliation":[{"name":"Prenatal Diagnosis &amp; Fetal Medicine Department Human Genetics and Genome Research Institute, National Research Centre  Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julian","family":"Nevado","sequence":"additional","affiliation":[{"name":"CIBERER\u2010Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras  Madrid Spain"},{"name":"Instituto de Gen\u00e9tica M\u00e9dica y Molecular (INGEMM)\u2010IdiPAZ Hospital Universitario La Paz  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Belinda","family":"Campos\u2010Xavier","sequence":"additional","affiliation":[{"name":"Service of Medical Genetics, Laboratoire de Maladies Mol\u00e9culaires, CHUV Centre Hospitalier Universitaire Vaudois  Lausanne Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lova S.","family":"Matsa","sequence":"additional","affiliation":[{"name":"Genomic Precision Diagnostic Department Igenomix  Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecilia","family":"Giunta","sequence":"additional","affiliation":[{"name":"Connective Tissue Unit, Division of Metabolism and Children's Research Center University Children's Hospital Zurich and University of Zurich  Zurich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pablo","family":"Lapunzina","sequence":"additional","affiliation":[{"name":"CIBERER\u2010Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras  Madrid Spain"},{"name":"Instituto de Gen\u00e9tica M\u00e9dica y Molecular (INGEMM)\u2010IdiPAZ Hospital Universitario La Paz  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor L.","family":"Ruiz\u2010Perez","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas Sols\u2010Morreale Consejo Superior de Investigaciones Cient\u00edficas\u2010Universidad Aut\u00f3noma de Madrid  Madrid Spain"},{"name":"CIBERER\u2010Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras  Madrid Spain"},{"name":"Instituto de Gen\u00e9tica M\u00e9dica y Molecular (INGEMM)\u2010IdiPAZ Hospital Universitario La Paz  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ebtesam","family":"Abdalla","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Medical Research Institute Alexandria University  Alexandria Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,10,15]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)00728-X"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2018.10.026"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2018.09.024"},{"key":"e_1_2_8_5_1","volume-title":"COL1A1\u2010 and COL1A2\u2010Related Osteogenesis Imperfecta. 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