{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T06:00:55Z","timestamp":1788242455509,"version":"build-2803163510"},"reference-count":24,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2012,2,17]],"date-time":"2012-02-17T00:00:00Z","timestamp":1329436800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2012,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>X\u2010linked hydrocephalus (XLH) has an incidence of 1\/30,000 male births and is characterized by intellectual disability, spastic paraplegia, adducted thumbs, and agenesis of corpus callosum, and\/or corticospinal tract. The great proportion of cases is ascribed to loss of function mutations of <jats:italic>L1CAM<\/jats:italic> gene. Hirschsprung disease (HSCR) is characterized by the absence of ganglion cells in the submucosal and myenteric plexuses along a variable portion of the intestinal tract and has incidence of about 1\/5,000. Although with several genes involved in its pathogenesis, the major HSCR gene is the <jats:italic>RET<\/jats:italic> proto\u2010oncogene. To date only a few patients have been reported with both phenotypes and mutations in the <jats:italic>L1CAM<\/jats:italic> gene. In this report, we describe a new patient with concurrent XLH and HSCR. <jats:italic>L1CAM<\/jats:italic> mutational screening showed the presence of the G698R hemizygous mutation, which is a deleterious substitution affecting a key residue necessary for the correct folding of the protein. Moreover, the patient also carried the transcriptional enhancer <jats:italic>RET<\/jats:italic> mutation (c.73\u2009+\u20099277T\u2009&gt;\u2009C) in heterozygosis. We speculate that both the <jats:italic>RET<\/jats:italic> enhancer variant, and the <jats:italic>L1CAM<\/jats:italic> mutation may act in combination to produce the enteric phenotype, probably with the participation of other still unidentified molecular events. While it is obvious that additional studies are necessary to further delineate the association between XLH and HSCR in the presence of <jats:italic>L1CAM<\/jats:italic> mutations, the documentation of this new patient reinforces the role of this gene acting either in a direct or indirect way in the pathogenesis of Hirschsprung disease. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.35244","type":"journal-article","created":{"date-parts":[[2012,2,17]],"date-time":"2012-02-17T20:02:27Z","timestamp":1329508947000},"page":"816-820","source":"Crossref","is-referenced-by-count":14,"title":["Association of X\u2010linked hydrocephalus and Hirschsprung disease: Report of a new patient with a mutation in the <i>L1CAM<\/i> gene"],"prefix":"10.1002","volume":"158A","author":[{"given":"Raquel M.","family":"Fern\u00e1ndez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roc\u00edo","family":"N\u00fa\u00f1ez\u2010Torres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lutgardo","family":"Garc\u00eda\u2010D\u00edaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Carlos","family":"de Agust\u00edn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo","family":"Anti\u00f1olo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salud","family":"Borrego","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,2,17]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2007.053959"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.01.002"},{"key":"e_1_2_6_4_1","first-page":"6231","volume-title":"The metabolic and molecular bases of inherited disease","author":"Chakravarti A","year":"2002"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.1.1"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3468(98)90169-5"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(1998)11:3<222::AID-HUMU7>3.0.CO;2-J"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03467"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.06.007"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2004.023960"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-11-137"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2008.191"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.39.3.e11"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00383-009-2420-0"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00383-006-1655-2"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpedsurg.2007.12.069"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3468(67)80085-X"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.34.8.670"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10038-004-0153-4"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.10185"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.gim.0000245632.06064.f1"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-010-0714-2"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.1380110189"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2010.08.006"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.2011.01692.x"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.35244","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.35244","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T08:39:48Z","timestamp":1697618388000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.35244"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,2,17]]},"references-count":24,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2012,4]]}},"alternative-id":["10.1002\/ajmg.a.35244"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.35244","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,2,17]]}}}