{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T13:30:43Z","timestamp":1791639043896,"version":"4.3.4"},"reference-count":15,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2016,9,9]],"date-time":"2016-09-09T00:00:00Z","timestamp":1473379200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Develop Med Child Neuro"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:p>Inherited aberrancies in intracellular vesicular transport are associated with a variety of neurological and non\u2010neurological diseases. <jats:italic><jats:styled-content style=\"fixed-case\">RUSC<\/jats:styled-content>2<\/jats:italic> is a gene found on chromosome 9p13.3 that codes for iporin, a ubiquitous protein with high expression in the brain that interacts with Rab proteins (<jats:styled-content style=\"fixed-case\">GTP<\/jats:styled-content>ases implicated in intracellular protein trafficking). Although mutations in Rab proteins have been described as causing brain abnormalities and intellectual disability, until now no disease\u2010causing mutations in <jats:italic><jats:styled-content style=\"fixed-case\">RUSC<\/jats:styled-content>2<\/jats:italic> have ever been reported in humans. We describe, to our knowledge for the first time, three patients with inherited homozygous nonsense mutations identified in <jats:italic><jats:styled-content style=\"fixed-case\">RUSC<\/jats:styled-content>2<\/jats:italic> on whole\u2010exome sequencing. All three patients had central hypotonia, microcephaly, and moderate to severe intellectual disability. Two patients had additional features of early\u2010onset epilepsy and absence of the splenium. This report adds to the ever\u2010expanding landscape of genetic causes of intellectual disability and increases our understanding of the cellular processes underlying this important neurological entity.<\/jats:p>","DOI":"10.1111\/dmcn.13250","type":"journal-article","created":{"date-parts":[[2016,9,9]],"date-time":"2016-09-09T21:00:52Z","timestamp":1473454852000},"page":"1317-1322","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Loss\u2010of\u2010function mutation in <i>RUSC2<\/i> causes intellectual disability and secondary microcephaly"],"prefix":"10.1111","volume":"58","author":[{"given":"Ali H","family":"Alwadei","sequence":"first","affiliation":[{"name":"Pediatric Neurology Department National Neuroscience Institute King Fahad Medical City Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruba","family":"Benini","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology Montreal Children's Hospital Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adel","family":"Mahmoud","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Department National Neuroscience Institute King Fahad Medical City Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Alasmari","sequence":"additional","affiliation":[{"name":"Medical Genetics Division Specialized Children's Hospital King Fahad Medical City Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik\u2010Jan","family":"Kamsteeg","sequence":"additional","affiliation":[{"name":"Genome Diagnostics Nijmegen Department of Medical Genetics Radboud University Medical Center Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Majid","family":"Alfadhel","sequence":"additional","affiliation":[{"name":"Genetics Division Department of Pediatrics King Saud bin Abdulaziz University for Health Science King Abdulaziz Medical City Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,9,9]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ridd.2010.12.018"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3999"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2014.02.015"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2001-2-5-reviews3007"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(01)29065-X"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-008-0740-z"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2013.12.009"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2007.050294"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/dnares\/4.2.141"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2121-6-15"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(01)00077-X"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22450"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.115.1.31"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e06-10-0886"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-015-1632-8"}],"container-title":["Developmental Medicine &amp; 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