{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T06:42:34Z","timestamp":1780555354863,"version":"3.54.1"},"reference-count":20,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,4,24]],"date-time":"2018-04-24T00:00:00Z","timestamp":1524528000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Autosomal recessive intellectual disability (<jats:styled-content style=\"fixed-case\">ARID<\/jats:styled-content>) is vastly heterogeneous. Truncating mutations of <jats:italic><jats:styled-content style=\"fixed-case\">TRAPPC<\/jats:styled-content>9<\/jats:italic> were reported in 8 <jats:styled-content style=\"fixed-case\">ARID<\/jats:styled-content> families. Autosomal recessive primary microcephaly (<jats:styled-content style=\"fixed-case\">MCPH<\/jats:styled-content>) represents another subgroup of <jats:styled-content style=\"fixed-case\">ARID<\/jats:styled-content>, itself very heterogeneous, where the size of the brain is very small since birth. <jats:italic><jats:styled-content style=\"fixed-case\">MCPH<\/jats:styled-content>1<\/jats:italic> plays a role at the centrosome via a <jats:styled-content style=\"fixed-case\">BRCT<\/jats:styled-content>1 domain, and in <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> Damage Repair (<jats:styled-content style=\"fixed-case\">DDR<\/jats:styled-content>) via <jats:styled-content style=\"fixed-case\">BRCT<\/jats:styled-content>2 and <jats:styled-content style=\"fixed-case\">BRCT<\/jats:styled-content>3, and it is not clear which of these two mechanisms causes <jats:styled-content style=\"fixed-case\">MCPH<\/jats:styled-content> in man.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We studied the phenotype and sequenced the exome in two siblings with <jats:styled-content style=\"fixed-case\">MCPH<\/jats:styled-content> and their unaffected sister.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Homozygous mutations of <jats:italic><jats:styled-content style=\"fixed-case\">TRAPPC<\/jats:styled-content>9<\/jats:italic> (p.Leu178Pro) and of <jats:italic><jats:styled-content style=\"fixed-case\">MCPH<\/jats:styled-content>1<\/jats:italic> (p.Arg741X) were found in both affected siblings. Brain <jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content> showed anomalies previously associated with <jats:styled-content style=\"fixed-case\">TRAPPC<\/jats:styled-content>9 defects, supporting the implication of <jats:italic><jats:styled-content style=\"fixed-case\">TRAPPC<\/jats:styled-content>9<\/jats:italic> in the phenotype. Importantly, the asymptomatic sister with normal head size was homozygous for the <jats:italic><jats:styled-content style=\"fixed-case\">MCPH<\/jats:styled-content>1<\/jats:italic> truncating mutation and heterozygous for the <jats:italic><jats:styled-content style=\"fixed-case\">TRAPPC<\/jats:styled-content>9<\/jats:italic> mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The affected siblings represent the first <jats:styled-content style=\"fixed-case\">ARID<\/jats:styled-content> cases with a <jats:italic><jats:styled-content style=\"fixed-case\">TRAPPC<\/jats:styled-content>9<\/jats:italic> missense mutation and with microcephaly of prenatal onset of. Furthermore, their unaffected sister represents strong evidence that the lack of <jats:styled-content style=\"fixed-case\">MCPH<\/jats:styled-content>1 <jats:styled-content style=\"fixed-case\">BRCT<\/jats:styled-content>3 domain does not cause <jats:styled-content style=\"fixed-case\">MCPH<\/jats:styled-content> in man, supporting a bifunctional model of <jats:styled-content style=\"fixed-case\">MCPH<\/jats:styled-content>1 where the centrosomal function is involved in brain volumic development and not the <jats:styled-content style=\"fixed-case\">DDR<\/jats:styled-content> function.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.400","type":"journal-article","created":{"date-parts":[[2018,4,25]],"date-time":"2018-04-25T04:11:57Z","timestamp":1524629517000},"page":"660-665","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Phenotypes in siblings with homozygous mutations of <i><scp>TRAPPC<\/scp>9<\/i> and\/or <i><scp>MCPH<\/scp>1<\/i> support a bifunctional model of <scp>MCPH<\/scp>1"],"prefix":"10.1002","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2919-0664","authenticated-orcid":false,"given":"Sarah","family":"Duerinckx","sequence":"first","affiliation":[{"name":"Department of Medical Genetics H\u00f4pital Erasme and IRIBHM Universit\u00e9 Libre de Bruxelles Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marije","family":"Meuwissen","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Antwerp University Hospital Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Perazzolo","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics H\u00f4pital Erasme and IRIBHM Universit\u00e9 Libre de Bruxelles Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Desmyter","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics H\u00f4pital Erasme and IRIBHM Universit\u00e9 Libre de Bruxelles Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Pirson","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics H\u00f4pital Erasme and IRIBHM Universit\u00e9 Libre de Bruxelles Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Abramowicz","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics H\u00f4pital Erasme and IRIBHM Universit\u00e9 Libre de Bruxelles Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,4,24]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2011.09.012"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.806"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1291"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0040387"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-0869-4"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2012.08.010"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.2174\/18715273113129990105"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2892"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature19057"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2016.12.030"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10423"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-52891-9.00013-0"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.11.007"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2015.00092"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1212366109"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.307868"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009242"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2008.128"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0029995"}],"container-title":["Molecular Genetics &amp; 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