{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:02:26Z","timestamp":1787018546007,"version":"build-2736575974"},"reference-count":13,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T00:00:00Z","timestamp":1739923200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["532002382"],"award-info":[{"award-number":["532002382"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    (Likely) pathogenic variants in\n                    <jats:italic>NR2F1<\/jats:italic>\n                    are associated with Bosch\u2010Boonstra\u2010Schaaf optic atrophy syndrome (BBSOAS, OMIM #615722), a rare neurodevelopmental disorder. Patients present with a variety of symptoms, including intellectual disability, developmental delay, visual impairment, muscular hypotonia, seizures, and\/or autistic features. Since it was first described in 2014, the phenotype has steadily expanded. However, there is limited information regarding the natural course of the disorder. Here, we present data on genetic variants and phenotype development of 47 individuals who responded to our questionnaire. A questionnaire was developed to assess the phenotype more comprehensively and to better understand the course of symptoms. In addition, families sent medical documents and photographs. To investigate the genotype\u2010phenotype correlation in our cohort, we compared clinical features of two genotypically distinct groups (variants in the DNA\u2010binding domain (DBD,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200917) versus variants elsewhere in the gene (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200930)). We observed a range of common symptoms including developmental delay, muscular hypotonia, optic atrophy, nystagmus, strabismus, autistic features, and thin corpus callosum on brain MRI. Overall, more improvement than worsening was reported. Individuals with variants in the DBD showed a higher prevalence of severe clinical features, such as infantile spasms (46.7% vs. 3.8%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.002) or nonverbality (50% vs. 3.4%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0004), age at diagnosis was statistically significantly different between the two genotypic groups (mean 4.7\u2009years vs. 8.9\u2009years,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.048). Our study confirms characteristic clinical features of BBSOAS. Variants in the DBD are associated with a more severe clinical phenotype. We found no evidence that the disease progresses; rather, several symptoms are reported to improve over time. However, prospective longitudinal studies are needed to further investigate disease progression.\n                  <\/jats:p>","DOI":"10.1111\/cge.14731","type":"journal-article","created":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T01:01:02Z","timestamp":1740013262000},"page":"168-178","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The Natural Course of Bosch\u2010Boonstra\u2010Schaaf Optic Atrophy Syndrome"],"prefix":"10.1111","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9513-1474","authenticated-orcid":false,"given":"Ilia","family":"Valentin","sequence":"first","affiliation":[{"name":"Institute of Human Genetics University Heidelberg  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7531-3234","authenticated-orcid":false,"given":"Pilar","family":"Caro","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University Heidelberg  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Fischer","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University Heidelberg  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6909-0003","authenticated-orcid":false,"given":"Heiko","family":"Brennenstuhl","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University Heidelberg  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian P.","family":"Schaaf","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University Heidelberg  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,19]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61580"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.01.002"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcab162"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2016.18"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.24305"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2018.04.024"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.02600"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhaa137"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201910291"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11081260"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2021.767965"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10803-012-1621-x"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005403421141"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.14731","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T04:00:03Z","timestamp":1752638403000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.14731"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,19]]},"references-count":13,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1111\/cge.14731"],"URL":"https:\/\/doi.org\/10.1111\/cge.14731","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/CGE.14731\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14731\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14731\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14731\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14731\/v2\/response1","asserted-by":"object"}]},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,19]]},"assertion":[{"value":"2024-12-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}