{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T15:28:11Z","timestamp":1787758091186,"version":"build-2784847793"},"reference-count":16,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:p>\n                    Bosch\u2013Boonstra\u2013Schaaf optic atrophy syndrome (BBSOAS) is an extremely rare autosomal dominant disorder characterized by intellectual disability, developmental delay, seizures, hypotonia, hearing loss, and optic nerve atrophy. This syndrome is caused by loss-of-function variants in the nuclear receptor subfamily 2 group F member 1 (\n                    <jats:italic toggle=\"yes\">NR2F1<\/jats:italic>\n                    ) gene. To date, approximately 80 patients have been reported with BBSOAS. Here, we describe a 3-year-old infant with delayed development, intellectual disability, strabismus, nystagmus, and optic atrophy with well-characterized features associated with BBSOAS. Whole-exome sequencing revealed a novel heterozygous missense mutation (NM_005654.6:c.437G&gt;A, p.Cys146Tyr) in the\n                    <jats:italic toggle=\"yes\">NR2F1<\/jats:italic>\n                    gene. This missense variant is predicted to be deleterious by the protein prediction tools (SIFT, PolyPhen-2, and MutationTaster). To the best of our knowledge, this is the first patient with BBSOAS reported from Turkey.\n                  <\/jats:p>","DOI":"10.4103\/ijo.ijo_1061_22","type":"journal-article","created":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T06:28:32Z","timestamp":1657607312000},"page":"2762-2764","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":4,"title":["Novel NR2F1 variant identified by whole-exome sequencing in a patient with Bosch\u2013Boonstra\u2013Schaaf optic atrophy syndrome"],"prefix":"10.4103","volume":"70","author":[{"given":"Ayca","family":"Kocaaga","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Eski\u015fehir City Hospital, Eski\u015fehir, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sevgi","family":"Yimenicioglu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Eski\u015fehir City Hospital, Eski\u015fehir, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haluk H\u00fcseyin","family":"G\u00fcrsoy","sequence":"additional","affiliation":[{"name":"Department of Ophtalmology, Eskisehir Osmangazi University Hospital, Eski\u015fehir, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2022,6,30]]},"reference":[{"key":"B1-20240828","doi-asserted-by":"crossref","first-page":"103941","DOI":"10.1016\/j.ejmg.2020.103941","article-title":"Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) initially diagnosed as ALG6-CDG:Functional evidence for benignity of the ALG6 c.391T>C (p.Tyr131His) variant and further expanding the BBSOAS phenotype","volume":"63","author":"Starosta","year":"2020","journal-title":"Eur J Med Genet"},{"key":"B2-20240828","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1097\/PRA.0000000000000440","article-title":"Bosch-Boonstra-Schaaf optic atrophy syndrome presenting as new-onset psychosis in a 32-year-old man:A case report and literature review","volume":"26","author":"Hobbs","year":"2020","journal-title":"J Psychiatr Pract"},{"key":"B3-20240828","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1002\/ajmg.a.62569","article-title":"A severe case of Bosch-Boonstra-Schaaf optic atrophy syndrome with a novel description of coloboma and septo-optic dysplasia, owing to a start codon variant in the NR2F1 gene","volume":"188","author":"Gazdagh","year":"2022","journal-title":"Am J Med Genet Part A"},{"key":"B4-20240828","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1002\/humu.24305","article-title":"NR2F1 database:112 variants and 84 patients support refining the clinical synopsis of Bosch-Boonstra-Schaaf optic atrophy syndrome","volume":"43","author":"Billiet","year":"2022","journal-title":"Hum Mutat"},{"key":"B5-20240828","doi-asserted-by":"crossref","first-page":"a002162","DOI":"10.1101\/mcs.a002162","article-title":"Novel NR2F1 variants likely disrupt DNA binding:Molecular modeling in two cases, review of published cases, genotype-phenotype correlation, and phenotypic expansion of the Bosch-Boonstra-Schaaf optic atrophy syndrome","volume":"3","author":"Kaiwar","year":"2017","journal-title":"Cold Spring Harb Mol Case Stud"},{"key":"B6-20240828","doi-asserted-by":"crossref","first-page":"e10291","DOI":"10.15252\/emmm.201910291","article-title":"Mouse Nr2f1 haploinsufficiency unveils new pathological mechanisms of a human optic atrophy syndrome","volume":"11","author":"Bertacchi","year":"2019","journal-title":"EMBO Mol Med"},{"key":"B7-20240828","doi-asserted-by":"crossref","first-page":"767965","DOI":"10.3389\/fnmol.2021.767965","article-title":"Structural and functional aspects of the neurodevelopmental gene NR2F1:From animal models to human pathology","volume":"14","author":"Tocco","year":"2021","journal-title":"Front Mol Neurosci"},{"key":"B8-20240828","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1002\/ajmg.a.61580","article-title":"Phenotypic expansion of Bosch-Boonstra-Schaaf optic atrophy syndrome and further evidence for genotype-phenotype correlations","volume":"182","author":"Rech","year":"2020","journal-title":"Am J Med Genet. Part A"},{"key":"B9-20240828","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1080\/13816810.2020.1719520","article-title":"A de novo nonsense mutation in the N-terminal of ligand-binding domain of NR2F1 gene provoked a milder phenotype of BBSOAS","volume":"41","author":"Zou","year":"2020","journal-title":"Ophthalmic Genet"},{"key":"B10-20240828","doi-asserted-by":"crossref","first-page":"e1278","DOI":"10.1002\/mgg3.1278","article-title":"Missense NR2F1 variant in monozygotic twins affected with the Bosch-Boonstra-Schaaf optic atrophy syndrome","volume":"8","author":"Mio","year":"2020","journal-title":"Mol Genet Genomic Med"},{"key":"B11-20240828","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1038\/gim.2016.18","article-title":"The expanding clinical phenotype of Bosch-Boonstra-Schaaf optic atrophy syndrome:20 new cases and possible genotype-phenotype correlations","volume":"18","author":"Chen","year":"2016","journal-title":"Genet Med"},{"key":"B12-20240828","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.ncl.2010.03.005","article-title":"Nonglaucomatous optic atrophy","volume":"28","author":"Golnik","year":"2010","journal-title":"Neurologic Clinics"},{"key":"B13-20240828","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.4103\/0301-4738.145996","article-title":"Etiology and clinical profile of childhood optic nerve atrophy at a tertiary eye care center in South India","volume":"62","author":"Chinta","year":"2014","journal-title":"Indian J Ophthalmol"},{"key":"B14-20240828","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2147\/RRN.S125575","article-title":"Neonatal periventricular leukomalacia:Current perspectives","volume":"8","author":"Ahya","year":"2018","journal-title":"Res Reports in Neonatol"},{"key":"B15-20240828","doi-asserted-by":"crossref","first-page":"2","DOI":"10.22599\/bioj.88","article-title":"The significance of periventricular leukomalacia on ophthalmic outcome","volume":"12","author":"McDonnell","year":"2015","journal-title":"Br Irish Orthoptic J"},{"key":"B16-20240828","doi-asserted-by":"crossref","first-page":"992","DOI":"10.4103\/0301-4738.145990","article-title":"Neuro-ophthalmic manifestations of prematurity","volume":"62","author":"Chhablani","year":"2014","journal-title":"Indian J Ophthalmol"}],"container-title":["Indian Journal of Ophthalmology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/ijo.IJO_1061_22","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T15:04:02Z","timestamp":1787756642000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/ijo.IJO_1061_22"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,30]]},"references-count":16,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2022]]}},"URL":"https:\/\/doi.org\/10.4103\/ijo.ijo_1061_22","relation":{},"ISSN":["0301-4738","1998-3689"],"issn-type":[{"value":"0301-4738","type":"print"},{"value":"1998-3689","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,30]]},"assertion":[{"value":"2022-04-27","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-31","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}