{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T13:17:30Z","timestamp":1769692650287,"version":"3.49.0"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"23","license":[{"start":{"date-parts":[[2020,11,18]],"date-time":"2020-11-18T00:00:00Z","timestamp":1605657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Action de Recherche Concert\u00e9e"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,2,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Congenital hydrocephalus is a potentially devastating, highly heterogeneous condition whose genetic subset remains incompletely known. We here report a consanguineous family where three fetuses presented with brain ventriculomegaly and limb contractures and shared a very rare homozygous variant of KIDINS220, consisting of an in-frame deletion of three amino acids adjacent to the fourth transmembrane domain. Fetal brain imaging and autopsy showed major ventriculomegaly, reduced brain mass, and with no histomorphologic abnormalities. We demonstrate that the binding of KIDINS220 to TrkA is diminished by the deletion mutation. This family is the second that associates a KIDINS220 genetic variant with human ventriculomegaly and limb contractures, validating causality of the gene and indicating TrkA as a likely mediator of the phenotype.<\/jats:p>","DOI":"10.1093\/hmg\/ddaa245","type":"journal-article","created":{"date-parts":[[2020,11,15]],"date-time":"2020-11-15T20:07:28Z","timestamp":1605470848000},"page":"3757-3764","source":"Crossref","is-referenced-by-count":16,"title":["TrkA mediates effect of novel KIDINS220 mutation in human brain ventriculomegaly"],"prefix":"10.1093","volume":"29","author":[{"given":"Valerie","family":"Jacquemin","sequence":"first","affiliation":[{"name":"IRIBHM, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathieu","family":"Antoine","sequence":"additional","affiliation":[{"name":"IRIBHM, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Duerinckx","sequence":"additional","affiliation":[{"name":"IRIBHM, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"},{"name":"Neurology Department, H\u00f4pital Erasme, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annick","family":"Massart","sequence":"additional","affiliation":[{"name":"IRIBHM, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"},{"name":"Department of Nephrology, H\u00f4pital Universitaire d\u2019Anvers, 2650 Edegem, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Desir","sequence":"additional","affiliation":[{"name":"Human Genetics Center, Institute of Pathology and Genetics, 6041 Charleroi, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camille","family":"Perazzolo","sequence":"additional","affiliation":[{"name":"IRIBHM, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie","family":"Cassart","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, H\u00f4pitaux Iris Sud, 1050 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominique","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, H\u00f4pitaux Iris Sud, 1050 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Val\u00e9rie","family":"Segers","sequence":"additional","affiliation":[{"name":"Department of Anatomopathology, CHU Brugmann, 1020 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophie","family":"Lecomte","sequence":"additional","affiliation":[{"name":"Department of Anatomopathology, CHU Brugmann, 1020 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Abramowicz","sequence":"additional","affiliation":[{"name":"IRIBHM, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"},{"name":"Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabelle","family":"Pirson","sequence":"additional","affiliation":[{"name":"IRIBHM, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,11,18]]},"reference":[{"key":"2021020414460854300_ref1","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1007\/s00381-007-0324-7","article-title":"Hydrocephalus in children born in 1999-2002: epidemiology, outcome and ophthalmological findings","volume":"23","author":"Persson","year":"2007","journal-title":"Childs Nerv. 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Rep."},{"key":"2021020414460854300_ref38","doi-asserted-by":"crossref","first-page":"3554","DOI":"10.1242\/jcs.056473","article-title":"Kidins220\/ARMS downregulation by excitotoxic activation of NMDARs reveals its involvement in neuronal survival and death pathways","volume":"122","author":"L\u00f3pez-Men\u00e9ndez","year":"2009","journal-title":"J. Cell Sci."},{"key":"2021020414460854300_ref39","doi-asserted-by":"crossref","first-page":"6340","DOI":"10.1523\/JNEUROSCI.20-17-06340.2000","article-title":"Neurotrophins induce death of hippocampal neurons via the p75 receptor","volume":"20","author":"Friedman","year":"2000","journal-title":"J. Neurosci."},{"key":"2021020414460854300_ref40","doi-asserted-by":"crossref","first-page":"3273","DOI":"10.1523\/JNEUROSCI.18-09-03273.1998","article-title":"Competitive Signaling between TrkA and p75 nerve growth factor receptors determines cell survival","volume":"18","author":"Yoon","year":"1998","journal-title":"J. Neurosci."},{"key":"2021020414460854300_ref41","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/cdd.2011.141","article-title":"Kidins220\/ARMS mediates the integration of the neurotrophin and VEGF pathways in the vascular and nervous systems","volume":"19","author":"Cesca","year":"2012","journal-title":"Cell Death Differ."},{"key":"2021020414460854300_ref42","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1002\/humu.23948","article-title":"Digenic inheritance of human primary microcephaly delineates centrosomal and non-centrosomal pathways","volume":"41","author":"Duerinckx","year":"2020","journal-title":"Hum. Mutat."},{"key":"2021020414460854300_ref43","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1111\/cge.13189","article-title":"A targeted sequencing panel identifies rare damaging variants in multiple genes in the cranial neural tube defect, anencephaly","volume":"93","author":"Ishida","year":"2018","journal-title":"Clin. 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