| Literature DB >> 24462372 |
Daniëlle G M Bosch1, F Nienke Boonstra2, Claudia Gonzaga-Jauregui3, Mafei Xu4, Joep de Ligt5, Shalini Jhangiani6, Wojciech Wiszniewski7, Donna M Muzny6, Helger G Yntema8, Rolph Pfundt8, Lisenka E L M Vissers5, Liesbeth Spruijt9, Ellen A W Blokland10, Chun-An Chen11, Richard A Lewis12, Sophia Y Tsai4, Richard A Gibbs13, Ming-Jer Tsai4, James R Lupski14, Huda Y Zoghbi15, Frans P M Cremers10, Bert B A de Vries16, Christian P Schaaf17.
Abstract
Optic nerve atrophy and hypoplasia can be primary disorders or can result from trans-synaptic degeneration arising from cerebral visual impairment (CVI). Here we report six individuals with CVI and/or optic nerve abnormalities, born after an uneventful pregnancy and delivery, who have either de novo heterozygous missense mutations in NR2F1, also known as COUP-TFI, or deletions encompassing NR2F1. All affected individuals show mild to moderate intellectual impairment. NR2F1 encodes a nuclear receptor protein that regulates transcription. A reporter assay showed that missense mutations in the zinc-finger DNA-binding domain and the putative ligand-binding domain decrease NR2F1 transcriptional activity. These findings indicate that NR2F1 plays an important role in the neurodevelopment of the visual system and that its disruption can lead to optic atrophy with intellectual disability.Entities:
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Year: 2014 PMID： 24462372 PMCID： PMC3928641 DOI： 10.1016/j.ajhg.2014.01.002
Source DB: PubMed Journal: Am J Hum Genet ISSN： 0002-9297 Impact factor: 11.025