{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T18:06:27Z","timestamp":1779213987096,"version":"3.51.4"},"reference-count":44,"publisher":"American Society for Clinical Investigation","issue":"17","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["SFB1444"],"award-info":[{"award-number":["SFB1444"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["SFB 1444 (P04)"],"award-info":[{"award-number":["SFB 1444 (P04)"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,2]]},"abstract":"<jats:p>\n                    Congenital hydrocephalus is a life-threatening condition that might affect brain development by increasing the pressure on the brain parenchyma. Here, we describe 6 male patients from 1 family, all presenting with an isolated X-linked congenital hydrocephalus. Exome sequencing identified a likely pathogenic variant of angiomotin (\n                    <jats:italic>AMOT<\/jats:italic>\n                    ) that segregated with the phenotype in the extended family. We show that the variant, affecting the first methionine, translated into a shorter AMOT protein lacking 91 amino acids from the N-terminus. Mechanistically, we unraveled that the absence of the N-terminus leads to abnormally increased AMOT protein levels due to the loss of both the N-degron degradation signal and the tankyrase-binding domain. Altered degradation of AMOT disrupted the barrier integrity of the cells. Thus, the identified\n                    <jats:italic>AMOT<\/jats:italic>\n                    variant likely underlies the clinical presentation of isolated X-linked hydrocephalus in this family, and our data underscore the importance of tight regulation of AMOT protein level in the brain. AMOT now joins the list of genes involved in congenital hydrocephalus in humans. These findings are instrumental for the genetic counseling of affected families.\n                  <\/jats:p>","DOI":"10.1172\/jci179438","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T16:12:16Z","timestamp":1756829536000},"source":"Crossref","is-referenced-by-count":0,"title":["A pathogenic variant of AMOT leads to isolated X-linked congenital hydrocephalus due to N-terminal truncation"],"prefix":"10.1172","volume":"135","author":[{"given":"Nurcan","family":"Hastar","sequence":"first","affiliation":[{"name":"Institute for Chemistry and Biochemistry, Freie Universitaet Berlin, Berlin, Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hagit","family":"Daum","sequence":"additional","affiliation":[{"name":"Department of Genetics, Hadassah Hebrew Medical Center and the Faculty of Medicine, Jerusalem, Israel."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikoletta","family":"Kardos-T\u00f6r\u00f6k","sequence":"additional","affiliation":[{"name":"Institute for Chemistry and Biochemistry, Freie Universitaet Berlin, Berlin, Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gael","family":"Ganz","sequence":"additional","affiliation":[{"name":"Department of Genetics, Hadassah Hebrew Medical Center and the Faculty of Medicine, Jerusalem, Israel."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leon","family":"Obendorf","sequence":"additional","affiliation":[{"name":"Institute for Chemistry and Biochemistry, Freie Universitaet Berlin, Berlin, Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Vajkoczy","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery with Pediatric Neurosurgery, Charit\u00e9 Universit\u00e4tsmedizin, Berlin, Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Orly","family":"Elpeleg","sequence":"additional","affiliation":[{"name":"Department of Genetics, Hadassah Hebrew Medical Center and the Faculty of Medicine, Jerusalem, Israel."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petra","family":"Knaus","sequence":"additional","affiliation":[{"name":"Institute for Chemistry and Biochemistry, Freie Universitaet Berlin, Berlin, Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"232","published-online":{"date-parts":[[2025,9,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2014.06.002"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1186\/s40001-022-00798-6"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-017-0438-4"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/jgm.3180"},{"key":"B5"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51448"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(03)02338-2"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2443.2007.01066.x"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.02.045"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1101\/gad.432007"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E19-03-0179"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2005.02.001"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2006.05216.x"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1101\/gad.2000111"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20111983"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.09.014"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2408697121"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0202260"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04308-2"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.904"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2006.10.021"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaw4912"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.06.094"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e13-11-0701"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.152.6.1247"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10239"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00012.2016"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1186\/s43556-021-00043-2"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1097\/01.mop.0000133634.79661.cd"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.rbmo.2016.06.028"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2013.05.014"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(03)00204-5"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.518019"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.096230"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2417"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1097\/00006123-200005000-00038"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-79610-6"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1620\/tjem.252.199"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2748"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.4067\/S0716-97602012000300005"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2012-101294"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201606430"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-021-00844-7"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.11.3.1023"}],"container-title":["Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jci.org\/articles\/view\/179438\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T17:14:17Z","timestamp":1779210857000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jci.org\/articles\/view\/179438"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,2]]},"references-count":44,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2025,9,2]]},"published-print":{"date-parts":[[2025,9,2]]}},"alternative-id":["10.1172\/JCI179438"],"URL":"https:\/\/doi.org\/10.1172\/jci179438","relation":{},"ISSN":["1558-8238"],"issn-type":[{"value":"1558-8238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,2]]},"article-number":"e179438"}}