{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:51:26Z","timestamp":1790142686077,"version":"4.0.1"},"reference-count":36,"publisher":"S. Karger AG","issue":"3","license":[{"start":{"date-parts":[[2010,1,1]],"date-time":"2010-01-01T00:00:00Z","timestamp":1262304000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2010,1,1]],"date-time":"2010-01-01T00:00:00Z","timestamp":1262304000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Mol Syndromol"],"published-print":{"date-parts":[[2010]]},"abstract":"<jats:p>The etiology of non-syndromic hydrocephalus is poorly understood. Via positional cloning in a consanguineous family with autosomal recessive hydrocephalus we have now identified a homozygous splice site mutation in the &lt;i&gt;CCDC88C&lt;\/i&gt; gene as a novel cause of a complex hydrocephalic brain malformation. The only living patient showed normal psychomotor development at the age of 3 years and 3 months and her deceased aunt, who was assumed to suffer from the same condition, had mild mental retardation. The mutation in the affected patients, a homozygous substitution in the donor splice site of intron 29, resulted in a shorter transcript due to exclusion of exon 29 and loss of functional protein, as shown by Western blotting (p.S1591HfsX7). In normal human tissue panels, we found &lt;i&gt;CCDC88C&lt;\/i&gt; ubiquitously expressed, but most prominently in the fetal brain, especially in pons and cerebellum, while expression in the adult brain appeared to be restricted to cortex and medulla oblongata. &lt;i&gt;CCDC88C&lt;\/i&gt; encodes DAPLE (HkRP2), a Hook-related protein with a binding domain for the central Wnt signalling pathway protein Dishevelled. Targeted quantitative RT-PCR and expression profiling of 84 genes from the Wnt signalling pathway in peripheral blood from the index patient and her healthy mother revealed increased mRNA levels of &lt;i&gt;CCDC88C&lt;\/i&gt; indicating transcriptional upregulation. Due to loss of CCDC88C function \u03b2&lt;i&gt;-catenin (CTNNB1)&lt;\/i&gt; and the downstream target &lt;i&gt;LEF1&lt;\/i&gt; showed increased mRNA levels in the patient, but many genes from the Wnt pathway and transcriptional target genes showed reduced expression, which might be explained by a complex negative feedback loop. We have thus identified a further essential component of the Wnt signalling pathway in human brain development.<\/jats:p>","DOI":"10.1159\/000319859","type":"journal-article","created":{"date-parts":[[2017,4,18]],"date-time":"2017-04-18T21:35:43Z","timestamp":1492551343000},"page":"99-112","source":"Crossref","is-referenced-by-count":94,"title":["Disturbed Wnt Signalling due to a Mutation in CCDC88C Causes an Autosomal Recessive Non-Syndromic Hydrocephalus with Medial Diverticulum"],"prefix":"10.1159","volume":"1","author":[{"given":"A.B.","family":"Ekici","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Hilfinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Jatzwauk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.T.","family":"Thiel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Wenzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Lorenz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Boltshauser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.W.","family":"Goecke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Staatz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.J.","family":"Morris-Rosendahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Sticht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U.","family":"Hehr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Reis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Rauch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2010,9,14]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1093%2Fbioinformatics%2F17.8.742"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1002%2Fhumu.20561"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1038%2Fng0196-94"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1016%2FS0378-1119%2802%2900623-6"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1101%2Fgad.13.17.2218"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1038%2Fnature04170"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1196%2Fannals.1377.016"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.ejpn.2009.03.005"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1038%2F75514"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1038%2Fng1005-1015"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1093%2Fbioinformatics%2Fbti571"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.cub.2005.05.054"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1128%2FMCB.23.4.1379-1389.2003"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.mod.2005.05.003"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1136%2Fjmg.2008.063818"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1146%2Fannurev.cellbio.20.010403.113126"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1038%2Fnature756"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1002%2Fajmg.a.32264"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1093%2Fcercor%2Fbhi077"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1086%2F301904"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1111%2Fj.1365-2443.2003.00692.x"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1136%2Fjmg.2005.032029"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1073%2Fpnas.94.7.2859"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1126%2Fscience.1151174"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1016%2FS0092-8674%2800%2980531-0"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1002%2F%28SICI%291096-9926%28199907%2960%3A1%3C22%3A%3AAID-TERA7%3E3.0.CO%3B2-6"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1186%2Fgb-2004-5-5-r36"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1007%2Fs004310050830"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1007%2Fs002340100567"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1073%2Fpnas.220158597"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1073%2Fpnas.1000395107"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1007%2Fs10048-009-0203-3"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.1093%2Fbioinformatics%2Fbth488"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.1136%2Fjmg.2009.071688"},{"key":"ref35","doi-asserted-by":"publisher","DOI":"10.1016%2FS0092-8674%2800%2981208-8"},{"key":"ref36","doi-asserted-by":"publisher","DOI":"10.1007%2Fs00415-006-0245-5"}],"container-title":["Molecular 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