{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:41:12Z","timestamp":1772160072185,"version":"3.50.1"},"reference-count":10,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,9,7]],"date-time":"2022-09-07T00:00:00Z","timestamp":1662508800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["#309782\/2020\u20101"],"award-info":[{"award-number":["#309782\/2020\u20101"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Biallelic loss\u2010of\u2010function variants in the\n                    <jats:italic>TBC1D2B<\/jats:italic>\n                    gene were recently reported as a cause of a neurodevelopmental disorder with seizures and gingival overgrowth. Here, we report two male siblings with the similar clinical characteristics. They started with gingival overgrowth and bilateral growth of soft tissues in the malar region at 3\u2009years of age, which evolved with significant maxillary hypertrophy and compression of the brainstem due to fibrous dysplasia of facial bones. After disease evolution, they presented with mental deterioration, limb tremors, and gait ataxia. One of them also presented with seizures. Whole exome sequencing revealed a novel biallelic frameshift variant [c.595del; p.(Val199Trpfs*22)] in the\n                    <jats:italic>TBC1D2B<\/jats:italic>\n                    gene in both patients, which was confirmed and found in heterozygous state in each of their parents. There are strong similarities in clinical characteristics, age of onset, and evolution between the patients described here and cases reported in the literature, including cherubism\u2010like phenotype with progressive gingival overgrowth and seizures. This is the fourth family in the world in which a biallelic loss\u2010of\u2010function variant in the\n                    <jats:italic>TBC1D2B<\/jats:italic>\n                    gene is associated with this phenotype. These results support that loss of TBC1D2B is the cause of this rare condition.\n                  <\/jats:p>","DOI":"10.1111\/cge.14215","type":"journal-article","created":{"date-parts":[[2022,8,27]],"date-time":"2022-08-27T06:04:07Z","timestamp":1661580247000},"page":"537-542","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Biallelic frameshift variant in the\n                    <scp>\n                      <i>TBC1D2B<\/i>\n                    <\/scp>\n                    gene in two siblings with progressive gingival overgrowth, fibrous dysplasia of face, and mental deterioration"],"prefix":"10.1111","volume":"102","author":[{"given":"Gabriela Rold\u00e3o","family":"Correia\u2010Costa","sequence":"first","affiliation":[{"name":"Department of Translational Medicine \u2013 Laboratory of Human Cytogenetics and Cytogenomics, School of Medical Sciences State University of Campinas  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"de Leeuw","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rolph","family":"Pfundt","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Il\u00e1ria Cristina","family":"Sgardioli","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine \u2013 Laboratory of Human Cytogenetics and Cytogenomics, School of Medical Sciences State University of Campinas  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Paula","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine \u2013 Laboratory of Human Cytogenetics and Cytogenomics, School of Medical Sciences State University of Campinas  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marilza","family":"de Lima Santos","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine \u2013 Laboratory of Human Cytogenetics and Cytogenomics, School of Medical Sciences State University of Campinas  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vera L\u00facia","family":"Gil\u2010da\u2010Silva\u2010Lopes","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine \u2013 Laboratory of Human Cytogenetics and Cytogenomics, School of Medical Sciences State University of Campinas  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T\u00e1rsis Paiva","family":"Vieira","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine \u2013 Laboratory of Human Cytogenetics and Cytogenomics, School of Medical Sciences State University of Campinas  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,9,7]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010021\u201003592\u20102"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20100854.2010.01038.x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells5010007"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006062"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2017.09.015"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23694"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.24071"},{"key":"e_1_2_9_9_1","doi-asserted-by":"crossref","unstructured":"Correia\u2010costaGR SgardioliIC PaulaA et al.Increased runs of homozygosity in the autosomal genome of Brazilian individuals with neurodevelopmental delay\/intellectual disability and\/or multiple congenital anomalies investigated by chromosomal microarray analysis.2022;45:1 e20200480\u20106.","DOI":"10.1590\/1678-4685-gmb-2020-0480"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4352"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature19057"}],"container-title":["Clinical 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