{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T22:25:39Z","timestamp":1793226339645,"version":"4.5.0"},"reference-count":11,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,8,6]],"date-time":"2019-08-06T00:00:00Z","timestamp":1565049600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2013\/11\/B\/NZ7\/04944"],"award-info":[{"award-number":["2013\/11\/B\/NZ7\/04944"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["NZ7"],"award-info":[{"award-number":["NZ7"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Retinoid acid receptors (RAR) are transcription factors that bind retinoic acid (RA), a metabolite of vitamin A. RARs are composed of three subunits encoded by\n                    <jats:italic>RARA, RARB<\/jats:italic>\n                    and\n                    <jats:italic>RARG<\/jats:italic>\n                    . In humans,\n                    <jats:italic>RARB<\/jats:italic>\n                    defects cause syndromic microphthalmia. So far, no germline pathogenic variants have been identified in\n                    <jats:italic>RARA<\/jats:italic>\n                    or\n                    <jats:italic>RARG<\/jats:italic>\n                    . We describe a girl with a de novo mutation NM_000964 c.826C\u2009&gt;\u2009T (p.Arg276Trp) in\n                    <jats:italic>RARA<\/jats:italic>\n                    with symptoms overlapping those described in\n                    <jats:italic>RARB<\/jats:italic>\n                    patients (coloboma, muscular hypotonia, dilated pulmonary artery, ectopic kidney). RARA Arg276 residue is functionally important, as it was previously shown that its substitution for Ala or Gln causes a 50\u2010 or 21\u2010fold impairment of RA binding, respectively. Moreover, in leukemic cells, the p.Arg611Trp mutation in a chimeric\n                    <jats:italic>PML\/RARA<\/jats:italic>\n                    gene (corresponding to the\n                    <jats:italic>RARA<\/jats:italic>\n                    p.Arg276Trp detected in our patient) conferred resistance to therapy by decreasing binding of all\u2010\n                    <jats:italic>trans<\/jats:italic>\n                    RA. The functional effect of\n                    <jats:italic>RARA<\/jats:italic>\n                    p.Arg276Trp was further confirmed by in silico modeling which showed that binding of RA by the Trp276 variant was similarly defective as in the deleterious model Ala276 mutant. We propose that RARA p.Arg276Trp causes the disease by affecting RA interaction with the RARA receptor.\n                  <\/jats:p>","DOI":"10.1111\/cge.13611","type":"journal-article","created":{"date-parts":[[2019,7,25]],"date-time":"2019-07-25T11:58:12Z","timestamp":1564055892000},"page":"371-375","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Syndromic chorioretinal coloboma associated with heterozygous de novo\n                    <i>RARA<\/i>\n                    mutation affecting an amino acid critical for retinoic acid interaction"],"prefix":"10.1111","volume":"96","author":[{"given":"Anna","family":"Jakubiuk\u2010Tomaszuk","sequence":"first","affiliation":[{"name":"Department of Pediatric Neurology and Rehabilitation Medical University of Bialystok  Bialystok Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Murcia Pienkowski","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Medical University of Warsaw  Warsaw Poland"},{"name":"Postgraduate School of Molecular Medicine Medical University of Warsaw  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szymon","family":"Zietkiewicz","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology Intercollegiate Faculty of Biotechnology UG\u2010MUG, University of Gdansk  Gdansk Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u0142gorzata","family":"Rydzanicz","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Medical University of Warsaw  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Kosi\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Medical University of Warsaw  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Stawi\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Medical University of Warsaw  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micha\u0142","family":"Szumi\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Pediatric Ophthalmology Medical University of Bialystok  Bialystok Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6286-5526","authenticated-orcid":false,"given":"Rafa\u0142","family":"P\u0142oski","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Medical University of Warsaw  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,8,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.08.014"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23004"},{"issue":"30","key":"e_1_2_9_4_1","doi-asserted-by":"crossref","first-page":"19516","DOI":"10.1016\/S0021-9258(17)32199-3","article-title":"Arg269 and Lys220 of retinoic acid receptor\u2010beta are important for the binding of retinoic acid","volume":"269","author":"Tairis N","year":"1994","journal-title":"J Biol 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