{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:15:00Z","timestamp":1790640900137,"version":"4.1.0"},"reference-count":31,"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":[[2017,11]]},"abstract":"<jats:p>Bosch\u2013Boonstra\u2013Schaaf optic atrophy syndrome (BBSOAS) is a recently described autosomal dominant disorder caused by mutations in the <jats:italic>NR2F1<\/jats:italic> gene. There are presently 28 cases of BBSOAS described in the literature. Its common features include developmental delay, intellectual disability, hypotonia, optic nerve atrophy, attention deficit disorder, autism spectrum disorder, seizures, hearing defects, spasticity, and thinning of the corpus callosum. Here we report two unrelated probands with novel, de novo, missense variants in <jats:italic>NR2F1<\/jats:italic>. The first is a 14-yr-old male patient with hypotonia, intellectual disability, optic nerve hypoplasia, delayed bone age, short stature, and altered neurotransmitter levels on cerebrospinal fluid testing. The second is a 5-yr-old female with severe developmental delay, motor and speech delay, and repetitive motion behavior. Whole-exome sequencing identified a novel missense <jats:italic>NR2F1<\/jats:italic> variant in each case, Cys86Phe in the DNA-binding domain in Case 1, and a Leu372Pro in the ligand-binding domain in Case 2. The presence of clinical findings compatible with BBSOAS along with structural analysis at atomic resolution using homology-based molecular modeling and molecular dynamic simulations, support the pathogenicity of these variants for BBSOAS. Short stature, abnormal CNS neurotransmitters, and macrocephaly have not been previously reported for this syndrome and may represent a phenotypic expansion of BBSOAS. A review of published cases along with new evidence from this report support genotype\u2013phenotype correlations for this disorder.<\/jats:p>","DOI":"10.1101\/mcs.a002162","type":"journal-article","created":{"date-parts":[[2017,9,30]],"date-time":"2017-09-30T00:25:28Z","timestamp":1506731128000},"page":"a002162","source":"Crossref","is-referenced-by-count":40,"title":["Novel <i>NR2F1<\/i> variants likely disrupt DNA binding: molecular modeling in two cases, review of published cases, genotype\u2013phenotype correlation, and phenotypic expansion of the Bosch\u2013Boonstra\u2013Schaaf optic atrophy syndrome"],"prefix":"10.1101","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0862-9538","authenticated-orcid":false,"given":"Charu","family":"Kaiwar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael T.","family":"Zimmermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Ferber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyv","family":"Niu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raul A.","family":"Urrutia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric W.","family":"Klee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dusica","family":"Babovic-Vuksanovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[2017,9,28]]},"reference":[{"key":"2021112506135596000_3.6.a002162.1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"2021112506135596000_3.6.a002162.2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35650"},{"key":"2021112506135596000_3.6.a002162.3","doi-asserted-by":"publisher","DOI":"10.1038\/nn1958"},{"key":"2021112506135596000_3.6.a002162.4","unstructured":"BIOVIA. 2017. 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