{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T21:24:17Z","timestamp":1753737857605},"reference-count":24,"publisher":"Cold Spring Harbor Laboratory","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cold Spring Harb Mol Case Stud"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:p>Thrombocytopenia-absent radii (TAR) syndrome, characterized by neonatal thrombocytopenia and bilateral radial aplasia with thumbs present, is typically caused by the inheritance of a 1q21.1 deletion and a single-nucelotide polymorphism in <jats:italic>RBM8A<\/jats:italic> on the nondeleted allele. We evaluated two siblings with TAR-like dysmorphology but lacking thrombocytopenia in infancy. Family NCI-107 participated in an IRB-approved cohort study and underwent comprehensive clinical and genomic evaluations, including aCGH, whole-exome, whole-genome, and targeted sequencing. Gene expression assays and electromobility shift assays (EMSAs) were performed to evaluate the variant of interest. The previously identified TAR-associated 1q21.1 deletion was present in the affected siblings and one healthy parent. Multiple sequencing approaches did not identify previously described TAR-associated SNPs or mutations in relevant genes. We discovered rs61746197 A &gt; G heterozygosity in the parent without the deletion and apparent hemizygosity in both siblings. rs61746197 A &gt; G overlaps a RelA\u2013p65 binding motif, and EMSAs indicate the A allele has higher transcription factor binding efficiency than the G allele. Stimulation of K562 cells to induce megakaryocyte differentiation abrogated the shift of both reference and alternative probes. The 1q21.1 TAR-associated deletion in combination with the G variant of rs61746197 on the nondeleted allele is associated with a TAR-like phenotype. rs61746197 G could be a functional enhancer\/repressor element, but more studies are required to identify the specific factor(s) responsible. Overall, our findings suggest a role of rs61746197 A &gt; G and human disease in the setting of a 1q21.1 deletion on the other chromosome.<\/jats:p>","DOI":"10.1101\/mcs.a004564","type":"journal-article","created":{"date-parts":[[2019,12,13]],"date-time":"2019-12-13T19:35:24Z","timestamp":1576265724000},"page":"a004564","source":"Crossref","is-referenced-by-count":5,"title":["1q21.1 deletion and a rare functional polymorphism in siblings with thrombocytopenia-absent radius\u2013like phenotypes"],"prefix":"10.1101","volume":"5","author":[{"given":"Seth A.","family":"Brodie","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean Paul","family":"Rodriguez-Aulet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neelam","family":"Giri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jieqiong","family":"Dai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mia","family":"Steinberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua J.","family":"Waterfall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Roberson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bari J.","family":"Ballew","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiyin","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah L.","family":"Anzick","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yonghong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuelin J.","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul S.","family":"Meltzer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Boland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Blanche P.","family":"Alter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharon A.","family":"Savage","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"246","published-online":{"date-parts":[[2019,12,13]]},"reference":[{"key":"2021112406080318000_5.6.a004564.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2007.01.018"},{"key":"2021112406080318000_5.6.a004564.2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.1083"},{"key":"2021112406080318000_5.6.a004564.3","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2017.178111"},{"key":"2021112406080318000_5.6.a004564.4","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-013-1265-8"},{"key":"2021112406080318000_5.6.a004564.5","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.39.12.876"},{"key":"2021112406080318000_5.6.a004564.6","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2653"},{"key":"2021112406080318000_5.6.a004564.7","doi-asserted-by":"publisher","DOI":"10.1097\/00005792-196948060-00001"},{"key":"2021112406080318000_5.6.a004564.8","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.14.4.2593"},{"key":"2021112406080318000_5.6.a004564.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2011.05.001"},{"key":"2021112406080318000_5.6.a004564.10","doi-asserted-by":"publisher","DOI":"10.1101\/531210"},{"key":"2021112406080318000_5.6.a004564.11","doi-asserted-by":"publisher","DOI":"10.1086\/510919"},{"key":"2021112406080318000_5.6.a004564.12","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23641"},{"key":"2021112406080318000_5.6.a004564.13","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.14913"},{"key":"2021112406080318000_5.6.a004564.14","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkj143"},{"key":"2021112406080318000_5.6.a004564.15","unstructured":"McDermott DA , Fong JC , Basson CT . 1993. 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