{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T15:00:13Z","timestamp":1790434813441,"version":"4.1.0"},"reference-count":22,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,3,30]],"date-time":"2017-03-30T00:00:00Z","timestamp":1490832000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"New York State Office of People with Developmental Disabilities"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:p><jats:italic><jats:styled-content style=\"fixed-case\">DOCK3<\/jats:styled-content><\/jats:italic> encodes the dedicator of cytokinesis 3 protein, a member of the <jats:styled-content style=\"fixed-case\">DOCK180<\/jats:styled-content> family of proteins that are characterized by guanine\u2010nucleotide exchange factor activity. <jats:italic><jats:styled-content style=\"fixed-case\">DOCK3<\/jats:styled-content><\/jats:italic> is expressed exclusively in the central nervous system and plays an important role in axonal outgrowth and cytoskeleton reorganization. <jats:italic>Dock3<\/jats:italic> knockout mice exhibit motor deficiencies with abnormal ataxic gait and impaired learning. We report 2 siblings with biallelic loss\u2010of\u2010function variants in <jats:italic><jats:styled-content style=\"fixed-case\">DOCK3<\/jats:styled-content><\/jats:italic>. Diagnostic whole\u2010exome sequencing (WES) and chromosomal microarray were performed on a proband with severe developmental disability, hypotonia, and ataxic gait. Testing was also performed on the proband's similarly affected brother. A paternally inherited 458\u2009kb deletion in chromosomal region 3p21.2 disrupting the <jats:italic><jats:styled-content style=\"fixed-case\">DOCK3<\/jats:styled-content><\/jats:italic> gene was identified in both affected siblings. WES identified a nonsense variant c.<jats:styled-content style=\"fixed-case\">382C<\/jats:styled-content>&gt;G (p.Gln128*) in the <jats:italic><jats:styled-content style=\"fixed-case\">DOCK3<\/jats:styled-content><\/jats:italic> gene (NM_004947) on the maternal allele in both siblings. Common features in both affected individuals include severe developmental disability, ataxic gait, and severe hypotonia, which recapitulates the <jats:italic>Dock3<\/jats:italic> knockout mouse phenotype. We show that complete <jats:italic><jats:styled-content style=\"fixed-case\">DOCK3<\/jats:styled-content><\/jats:italic> deficiency in humans leads to developmental disability with significant hypotonia and gait ataxia, probably due to abnormal axonal development.<\/jats:p>","DOI":"10.1111\/cge.12995","type":"journal-article","created":{"date-parts":[[2017,2,14]],"date-time":"2017-02-14T10:46:37Z","timestamp":1487069197000},"page":"430-433","source":"Crossref","is-referenced-by-count":25,"title":["Biallelic loss\u2010of\u2010function variants in <i><scp>DOCK3<\/scp><\/i> cause muscle hypotonia, ataxia, and intellectual disability"],"prefix":"10.1111","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8249-0549","authenticated-orcid":false,"given":"K.L.","family":"Helbig","sequence":"first","affiliation":[{"name":"Division of Clinical Genomics Ambry Genetics  Aliso Viejo California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Mroske","sequence":"additional","affiliation":[{"name":"Division of Clinical Genomics Ambry Genetics  Aliso Viejo California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Moorthy","sequence":"additional","affiliation":[{"name":"The George A. Jervis Clinic, New York State Institute for Basic Research in Developmental Disabilities  Staten Island New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.A.","family":"Sajan","sequence":"additional","affiliation":[{"name":"Division of Clinical Genomics Ambry Genetics  Aliso Viejo California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Velinov","sequence":"additional","affiliation":[{"name":"The George A. Jervis Clinic, New York State Institute for Basic Research in Developmental Disabilities  Staten Island New York"},{"name":"Department of Pediatrics Icahn School of Medicine at Mount Sinai  New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,3,30]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.162.6.1133"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ridd.2010.12.018"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genom-082509-141640"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3999"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14135"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1114194"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1312543"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.200"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3010076"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.40.10.733"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0914514107"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3985-08.2009"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2014.154"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature19057"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2013.91"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4884-11.2012"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M311275200"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-6606-6-22"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24073"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.677"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.07.013"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.04.012"}],"updated-by":[{"DOI":"10.1111\/cge.13212","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2018,4,14]],"date-time":"2018-04-14T00:00:00Z","timestamp":1523664000000}}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcge.12995","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.12995","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T14:55:07Z","timestamp":1695567307000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.12995"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3,30]]},"references-count":22,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2017,10]]}},"alternative-id":["10.1111\/cge.12995"],"URL":"https:\/\/doi.org\/10.1111\/cge.12995","archive":["Portico"],"relation":{"erratum":[{"id-type":"doi","id":"10.1111\/cge.13212","asserted-by":"object"}]},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3,30]]}}}