{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T11:45:18Z","timestamp":1781869518442,"version":"3.54.5"},"reference-count":64,"publisher":"American Society for Clinical Investigation","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,3,17]]},"abstract":"<jats:p>\n                    The 2p15p16.1 microdeletion syndrome has a core phenotype consisting of intellectual disability, microcephaly, hypotonia, delayed growth, common craniofacial features, and digital anomalies. So far, more than 20 cases of 2p15p16.1 microdeletion syndrome have been reported in the literature; however, the size of the deletions and their breakpoints vary, making it difficult to identify the candidate genes. Recent reports pointed to 4 genes (\n                    <jats:italic>XPO1<\/jats:italic>\n                    ,\n                    <jats:italic>USP34<\/jats:italic>\n                    ,\n                    <jats:italic>BCL11A<\/jats:italic>\n                    , and\n                    <jats:italic>REL<\/jats:italic>\n                    ) that were included, alone or in combination, in the smallest deletions causing the syndrome. Here, we describe 8 new patients with the 2p15p16.1 deletion and review all published cases to date. We demonstrate functional deficits for the above 4 candidate genes using patients\u2019 lymphoblast cell lines (LCLs) and knockdown of their orthologs in zebrafish. All genes were dosage sensitive on the basis of reduced protein expression in LCLs. In addition, deletion of\n                    <jats:italic>XPO1<\/jats:italic>\n                    , a nuclear exporter, cosegregated with nuclear accumulation of one of its cargo molecules (rpS5) in patients\u2019 LCLs. Other pathways associated with these genes (e.g., NF-\u03baB and Wnt signaling as well as the DNA damage response) were not impaired in patients\u2019 LCLs. Knockdown of\n                    <jats:italic>xpo1a<\/jats:italic>\n                    ,\n                    <jats:italic>rel<\/jats:italic>\n                    ,\n                    <jats:italic>bcl11aa<\/jats:italic>\n                    , and\n                    <jats:italic>bcl11ab<\/jats:italic>\n                    resulted in abnormal zebrafish embryonic development including microcephaly, dysmorphic body, hindered growth, and small fins as well as structural brain abnormalities. Our multifaceted analysis strongly implicates\n                    <jats:italic>XPO1<\/jats:italic>\n                    ,\n                    <jats:italic>REL<\/jats:italic>\n                    , and\n                    <jats:italic>BCL11A<\/jats:italic>\n                    as candidate genes for 2p15p16.1 microdeletion syndrome.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.85461","type":"journal-article","created":{"date-parts":[[2016,3,16]],"date-time":"2016-03-16T11:00:44Z","timestamp":1458126044000},"source":"Crossref","is-referenced-by-count":30,"title":["Identifying candidate genes for 2p15p16.1 microdeletion syndrome using clinical, genomic, and functional analysis"],"prefix":"10.1172","volume":"1","author":[{"given":"Hani","family":"Bagheri","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of British Columbia (UBC), Vancouver, British Columbia, Canada."},{"name":"Child and Family Research Institute, 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USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert S.","family":"Wildin","sequence":"additional","affiliation":[{"name":"St. Luke\u2019s Children\u2019s Hospital, Boise, Idaho, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malgorzata J.M.","family":"Nowaczyk","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, McMaster University Medical Centre, Hamilton, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Eichmeyer","sequence":"additional","affiliation":[{"name":"St. Luke\u2019s Mountain States Tumor Institute, Boise, Idaho, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Lehman","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, UBC, Vancouver, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Maranda","sequence":"additional","affiliation":[{"name":"Medical Genetics, Universit\u00e9 de Sherbrooke, Sherbrooke, Qu\u00e9bec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally","family":"Martell","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of British Columbia (UBC), Vancouver, British Columbia, Canada."},{"name":"Child and Family Research Institute, Vancouver, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianghong","family":"Shan","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, UBC, Vancouver, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne M.E.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, UBC, Vancouver, British Columbia, 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