{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T11:23:34Z","timestamp":1787397814727,"version":"build-2736575974"},"reference-count":32,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"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":["Epileptic Disorders"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate the diagnostic utility and genetic spectrum of next\u2010generation sequencing (NGS) in a large, well\u2010phenotyped cohort of Turkish pediatric patients with epilepsy of unknown etiology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Between January 2021 and December 2024, 250 children (115 female, 135 male) with unexplained epilepsy underwent either whole\u2010exome sequencing (WES;\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009104) or clinical exome sequencing (CES;\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009146). Variants were interpreted according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Clinical data, including seizure semiology, neuroimaging, EEG findings, and treatment response, were retrospectively reviewed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A definitive molecular diagnosis (pathogenic or likely pathogenic variants) was established in 89 patients (89\/250, 35.6%). Including variants of uncertain significance (VUS) with strong phenotypic correlation raised the diagnostic yield to 57.6% (144\/250). The genetic landscape was highly heterogeneous, involving 59 distinct genes.\n                      <jats:italic>SCN1A<\/jats:italic>\n                      was the most frequently implicated gene (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200911, 12.4% of diagnosed cases), followed by\n                      <jats:italic>MECP2<\/jats:italic>\n                      and\n                      <jats:italic>PRRT2<\/jats:italic>\n                      (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20095 each). Notably, the recurrent\n                      <jats:italic>PRRT2<\/jats:italic>\n                      c.649dup (p.Arg217Profs*8) frameshift variant was identified in four unrelated Turkish families. Inheritance patterns included autosomal dominant (56\/89, 63%), autosomal recessive (20\/89, 22%), and X\u2010linked (13\/89, 15%). Diagnostic yields were comparable between WES (38\/104, 36.5%) and CES (51\/146, 35%) (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.97). Neonatal\u2010onset epilepsy (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.03) and the presence of autistic features (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.04) were significantly associated with a positive genetic diagnosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our study confirms NGS as a first\u2010tier diagnostic tool in pediatric epilepsy, revealing a distinctive genetic architecture enriched with novel and population\u2010specific variants. These findings emphasize (1) a high diagnostic yield (\u223c36%) supporting first\u2010tier use of NGS; (2) a distinctive genetic architecture characterized by recurrent\n                      <jats:italic>PRRT2<\/jats:italic>\n                      variants and an elevated burden of autosomal recessive disorders, likely reflecting regional consanguinity patterns; and (3) a phenotype\u2010driven framework for prioritizing VUS re\u2010evaluation in clinical neurology practice. Such data from underrepresented populations are crucial for global genomic databases and directly inform precision medicine and genetic counseling.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epd2.70277","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T07:37:34Z","timestamp":1783064254000},"page":"1252-1273","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical utility and genetic landscape of exome sequencing in a large pediatric epilepsy cohort: Insights from a Turkish tertiary care center"],"prefix":"10.1002","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1874-0109","authenticated-orcid":false,"given":"Derya","family":"Karaer","sequence":"first","affiliation":[{"name":"Pamukkale University Faculty of Medicine Department of Medical Genetics  Denizli Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beste Kip\u00e7ak","family":"Y\u00fczba\u015f\u0131","sequence":"additional","affiliation":[{"name":"Pamukkale University, Faculty of Medicine Department of Pediatric Neurology  Denizli Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0130pek","family":"\u015eahin","sequence":"additional","affiliation":[{"name":"Pamukkale University Faculty of Medicine Department of Medical Genetics  Denizli Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olcay","family":"G\u00fcng\u00f6r","sequence":"additional","affiliation":[{"name":"Pamukkale University, Faculty of Medicine Department of Pediatric Neurology  Denizli Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1415-9103","authenticated-orcid":false,"given":"Kadri","family":"Karaer","sequence":"additional","affiliation":[{"name":"Pamukkale University Faculty of Medicine 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