{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T12:30:59Z","timestamp":1769603459153,"version":"3.49.0"},"reference-count":25,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,7,24]],"date-time":"2023-07-24T00:00:00Z","timestamp":1690156800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The L1 cell adhesion molecule (<jats:italic>L1CAM<\/jats:italic>, OMIM 308840<jats:italic>)<\/jats:italic> gene is primarily expressed in the nervous system and encodes the L1 adhesion molecule protein. Variations in <jats:italic>L1CAM<\/jats:italic> cause a wide spectrum of X\u2010linked neurological disorders summarized as the L1 syndrome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We report a 29\u2010year\u2010old pregnant woman who experienced multiple adverse pregnancy outcomes due to recurrent fetal hydrocephalus with an X\u2010linked recessive inheritance. Genomic DNA was extracted from the third aborted male fetus and analyzed via trio whole\u2010exome sequencing (WES). Total RNA was isolated from the pregnant woman to assess splicing variation at the mRNA level, and amniotic fluid was extracted from the woman for prenatal diagnosis on her fourth fetus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All four male fetuses were affected by severe hydrocephalus. We identified a maternally derived hemizygous splicing variation NM_000425.5:[c.3046\u2009+\u20091G\u2009&gt;\u2009A]; NP_000416.1 p.(Gly1016AspfsTer6) (chrX:153130275) in Intron 22 of the <jats:italic>L1CAM<\/jats:italic>. This variation disrupts the donor splice site and causes the retention of Intron 22, which results in frame shift and a premature termination codon at position 1021 with the ability to produce a truncated protein without the fifth fibronectin\u2010repeat III, transmembrane, and cytoplasmic domains or to induce the degradation of mRNAs by nonsense\u2010mediated mRNA decay. The same hemizygous variant was also detected in the amniocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This report enhances our knowledge of genetic and phenotypic characteristics of X\u2010linked fetal hydrocephalus, providing a new genetic basis for prenatal diagnosis and pre\u2010implantation prenatal diagnosis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2253","type":"journal-article","created":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T06:45:11Z","timestamp":1690267511000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A novel splicing variation in <i>L1CAM<\/i> is responsible for recurrent fetal hydrocephalus"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6855-6545","authenticated-orcid":false,"given":"Tiantian","family":"He","sequence":"first","affiliation":[{"name":"Department of Medical Genetics &amp; Prenatal Diagnosis Center West China Second University Hospital, Sichuan University  Chengdu China"},{"name":"Department of Obstetrics and Gynecology West China Second University Hospital, Sichuan University  Chengdu China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiang","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology West China Second University Hospital, Sichuan University  Chengdu China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bocheng","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics &amp; Prenatal Diagnosis Center West China Second University Hospital, Sichuan University  Chengdu China"},{"name":"Department of Obstetrics and Gynecology West China Second University Hospital, Sichuan University  Chengdu China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics &amp; Prenatal Diagnosis Center West China Second University Hospital, Sichuan University  Chengdu China"},{"name":"Department of Obstetrics and Gynecology West China Second University Hospital, Sichuan University  Chengdu China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jieni","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics &amp; Prenatal Diagnosis Center West China Second University Hospital, Sichuan University  Chengdu China"},{"name":"Department of Obstetrics and Gynecology West China Second University Hospital, Sichuan University  Chengdu China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingqing","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics &amp; Prenatal Diagnosis Center West China Second University Hospital, Sichuan University  Chengdu China"},{"name":"Department of Obstetrics and Gynecology West China Second University Hospital, Sichuan University  Chengdu China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Like","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics &amp; Prenatal Diagnosis Center West China Second University Hospital, Sichuan University  Chengdu China"},{"name":"Department of Obstetrics and Gynecology West China Second University Hospital, Sichuan University  Chengdu China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shanling","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics &amp; Prenatal Diagnosis Center West China Second University Hospital, Sichuan University  Chengdu China"},{"name":"Department of Obstetrics and Gynecology West China Second University Hospital, Sichuan University  Chengdu China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"He","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics &amp; Prenatal Diagnosis Center West China Second University Hospital, Sichuan University  Chengdu China"},{"name":"Department of Obstetrics and Gynecology West China Second University Hospital, Sichuan University  Chengdu China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuemei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics &amp; Prenatal Diagnosis Center West China Second University Hospital, Sichuan University  Chengdu China"},{"name":"Department of Obstetrics and Gynecology West China Second University Hospital, Sichuan University  Chengdu China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,7,24]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51448"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010013\u20101146\u20101"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2004.029538"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031\u2010016\u20100754\u20103"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(20000501)92:1<40::AID-AJMG7>3.0.CO;2-R"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2020.101999"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/jgm.3180"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.5550"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clineuro.2018.06.007"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3171\/ped.2006.105.5.403"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tjog.2020.03.022"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10038\u2010004\u20100153\u20104"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33803"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.proghi.2016.05.001"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018\u2010010\u20100339\u20101"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441\u2010012\u20101345\u20104"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/cga.12069"},{"key":"e_1_2_10_20_1","volume-title":"GeneReviews(\u00ae)","author":"Stumpel C.","year":"2021"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2019.00817"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.02.009"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00381\u2010020\u201004657\u20109"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2009.071688"},{"key":"e_1_2_10_25_1","first-page":"xvii","article-title":"Introduction. Cell adhesion molecules: Implications in neurological diseases","volume":"8","author":"Walmod P. S.","year":"2014","journal-title":"Advances in Neurobiology"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00381\u2010021\u201005213\u20109"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.2253","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T03:47:08Z","timestamp":1700279228000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.2253"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,24]]},"references-count":25,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2023,11]]}},"alternative-id":["10.1002\/mgg3.2253"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.2253","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,24]]},"assertion":[{"value":"2021-11-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2253"}}