{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T13:05:14Z","timestamp":1790168714139,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"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":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Familial cerebral cavernous malformation (CCM) is an autosomal dominant vascular disorder with age\u2010dependent penetrance and marked intrafamilial variability.\n                      <jats:italic>KRIT1<\/jats:italic>\n                      loss\u2010of\u2010function variants are the most common genetic cause, but pediatric genotype\u2013phenotype correlations remain limited.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Clinical, radiological, histopathological, and molecular findings of a pediatric family with suspected familial CCM were reviewed. Brain and spinal MRI, calvarial histopathology, whole\u2010exome sequencing, segregation analysis, and targeted literature review were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The index patient was a 14\u2010year\u2010old boy presenting with focal seizure and a progressively enlarging right parietal calvarial mass. MRI revealed multiple cerebral and cerebellar CCMs with a cervical intramedullary cavernous malformation. The calvarial lesion was excised and confirmed as hemangioma. Whole\u2010exome sequencing identified a previously unreported heterozygous\n                      <jats:italic>KRIT1<\/jats:italic>\n                      initiation\u2010region duplication, NM_004912.4: c.2dup, predicted to result in p.(Met1IlefsTer31) with loss of all major functional domains. The same variant was detected in the clinically asymptomatic sibling with MRI\u2010confirmed multiple CCMs, whereas the mother was negative. The father had died from intracerebral hemorrhage, but genetic testing was unavailable.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This report expands the\n                      <jats:italic>KRIT1<\/jats:italic>\n                      mutational spectrum and illustrates the wide clinical range of familial CCM, from asymptomatic radiological disease to epilepsy and fatal hemorrhage within one family. These findings support early molecular diagnosis, cascade screening, and susceptibility\u2010sensitive MRI surveillance.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.70304","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T05:29:17Z","timestamp":1789709357000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pediatric Familial Cerebral Cavernous Malformation Associated With a Novel\n                    <i>KRIT1<\/i>\n                    Initiation\u2010Region Frameshift Variant"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2112-8284","authenticated-orcid":false,"given":"\u00d6zlem","family":"Yay\u0131c\u0131 K\u00f6ken","sequence":"first","affiliation":[{"name":"Division of Pediatric Neurology, Department of Pediatrics Akdeniz University Faculty of Medicine  Antalya Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7035-6673","authenticated-orcid":false,"given":"Mehpare Sar\u0131","family":"Yanarta\u015f","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology, Department of Pediatrics Prof. Dr. S\u00fcleyman Yal\u00e7\u0131n City Hospital  \u0130stanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2188-893X","authenticated-orcid":false,"given":"Hande","family":"Ayg\u00fcn","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology, Department of Pediatrics Akdeniz University Faculty of Medicine  Antalya Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4938-3420","authenticated-orcid":false,"given":"Ahmet Cevdet","family":"Ceylan","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Y\u0131ld\u0131r\u0131m Beyaz\u0131t University Faculty of Medicine, Ankara Bilkent City Hospital  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2716-4422","authenticated-orcid":false,"given":"Kamil","family":"Karaali","sequence":"additional","affiliation":[{"name":"Department of Radiology Akdeniz University Faculty of Medicine  Antalya Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2192-4945","authenticated-orcid":false,"given":"Mehmet Saim","family":"Kazan","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Akdeniz University Faculty of Medicine  Antalya Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuros\/nyx091"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-010-0366-6"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fsurg.2016.00060"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcaf408"},{"key":"e_1_2_14_6_1","first-page":"189","volume-title":"Handbook of Vascular Malformations of the Brain","author":"Boulday G.","year":"2020"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00271890"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5200870"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2023.1184333"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000012852"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2010.00441.x"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10804"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00234-022-03056-y"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.30381"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2011.155"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(15)00303\u20108"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-021-00809-1"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2377-3-5"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg103"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-016-0806-8"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/pl00014581"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A4427"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-010-9360-y"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031\u2010021\u201001814\u2010w"},{"key":"e_1_2_14_25_1","article-title":"Molecular Genetic Analysis of Cerebral Cavernous Malformations: An Update","volume":"5","author":"Ricci C.","year":"2021","journal-title":"Vessel Plus"},{"key":"e_1_2_14_26_1","doi-asserted-by":"crossref","unstructured":"Riolo G. C.Ricci andS.Battistini.2021. \u201cMolecular Genetic Features of Cerebral Cavernous Malformations (CCM) Patients: An Overall View From Genes to Endothelial Cells.\u201d10 no.3:704.","DOI":"10.3390\/cells10030704"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00381-017-3434-x"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.23937\/2378-3656\/1410032"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.2000.6426"},{"key":"e_1_2_14_30_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20091258"},{"key":"e_1_2_14_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-017-0881-5"},{"key":"e_1_2_14_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-3240-5_4"},{"key":"e_1_2_14_33_1","doi-asserted-by":"publisher","DOI":"10.3345\/kjp.2016.59.6.280"},{"key":"e_1_2_14_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2020.525986"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.70304","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mgg3.70304","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.70304","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T12:29:13Z","timestamp":1790166553000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.70304"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":33,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/mgg3.70304"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.70304","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"2026-06-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70304"}}