{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T17:39:02Z","timestamp":1786469942836,"version":"build-2736575974"},"reference-count":15,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP25ek0109760"],"award-info":[{"award-number":["JP25ek0109760"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP25ek0109674"],"award-info":[{"award-number":["JP25ek0109674"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP25ek0109637"],"award-info":[{"award-number":["JP25ek0109637"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Human Genetics"],"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                      Pathogenic variants in\n                      <jats:italic>L1CAM<\/jats:italic>\n                      , located at Xq28, cause a spectrum of neurodevelopmental disorders of varying severity, including congenital hydrocephalus, MASA syndrome, agenesis of the corpus callosum, and intellectual disability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Material and Methods<\/jats:title>\n                    <jats:p>\n                      Exome sequencing (ES) and RNA studies using urine\u2011derived cells were performed in the younger sibling with agenesis of the corpus callosum, ventriculomegaly, and hearing impairment. A minigene assay was performed to quantitively evaluate the splicing impact of the\n                      <jats:italic>L1CAM<\/jats:italic>\n                      variant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified a deep intronic\n                      <jats:italic>L1CAM<\/jats:italic>\n                      variant (NM_001278116.2:c.1124\u201024T&gt;G) in Intron 10, for which SpliceAI predicts creation of a cryptic acceptor site (score 0.99) via introduction of an AG dinucleotide. The same\n                      <jats:italic>L1CAM<\/jats:italic>\n                      variant was also detected in the older affected brother. RNA studies using of urine\u2011derived cells UDCs demonstrated retention of a 23\u2011bp intronic segment in the transcripts, consistent with nonsense\u2011mediated decay (NMD). Specifically, TA\u2011cloning of reverse transcription PCR products detected the mutant allele in 2% of colonies, and RNA\u2011seq recovered the aberrant junction in only 5 of 18 reads. A minigene assay corroborated the mechanism, yielding a variant\u2010specific larger product corresponding to the 23\u2011bp retained sequence.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This report broadens the molecular spectrum of intronic\n                      <jats:italic>L1CAM<\/jats:italic>\n                      variants and underscores the practical value of non\u2011invasive, UDC\u2010based RNA testing in combination with complementary minigene assays for interpreting deep intronic variants.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ahg.70046","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T11:29:35Z","timestamp":1783423775000},"page":"278-282","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Utility of Urine\u2010Derived Cells for Characterizing Aberrant Splicing Caused by a Novel Deep Intronic\n                    <i>L1CAM<\/i>\n                    Variant"],"prefix":"10.1111","volume":"90","author":[{"given":"Takuma","family":"Harasaki","sequence":"first","affiliation":[{"name":"Department of Biochemistry Hamamatsu University School of Medicine  Hamamatsu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachiko","family":"Miyamoto","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Hamamatsu University School of Medicine  Hamamatsu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Yonekawa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Mie University  Tsu Mie Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaharu","family":"Isogai","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Hamamatsu University School of Medicine  Hamamatsu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuhiro","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Showa University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuko","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Hamamatsu University School of Medicine  Hamamatsu Japan"},{"name":"Division of Dermatology, Department of Internal Medicine, Faculty of Medicine Saga University  Saga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotomo","family":"Saitsu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Hamamatsu University School of Medicine  Hamamatsu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2023.11.009"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2777"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2005.07.015"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s10038\u2010023\u201001211\u20108"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.33.1.59"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010024\u201075020\u20100"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2021.701652"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460\u20102075.1984.tb01753.x"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2025.104378"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010018\u201006063\u2010x"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.119.6.1387"},{"key":"e_1_2_10_13_1","volume-title":"GeneReviews(\u00ae)","author":"Stumpel C.","year":"2004"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232112977"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2023.06.002"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1261\/rna.876308"}],"container-title":["Annals of Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ahg.70046","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/ahg.70046","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ahg.70046","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T16:52:52Z","timestamp":1786467172000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ahg.70046"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,7]]},"references-count":15,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1111\/ahg.70046"],"URL":"https:\/\/doi.org\/10.1111\/ahg.70046","archive":["Portico"],"relation":{},"ISSN":["0003-4800","1469-1809"],"issn-type":[{"value":"0003-4800","type":"print"},{"value":"1469-1809","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,7]]},"assertion":[{"value":"2025-12-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}