NR2F1 mutations cause optic atrophy with intellectual disability

Daniëlle G.M. Bosch, F. Nienke Boonstra, Claudia Gonzaga-Jauregui, Mafei Xu, Joep De Ligt, Shalini Jhangiani, Wojciech Wiszniewski, Donna M. Muzny, Helger G. Yntema, Rolph Pfundt, Lisenka E.L.M. Vissers, Liesbeth Spruijt, Ellen A.W. Blokland, Chun An Chen, Richard A. Lewis, Sophia Y. Tsai, Richard A. Gibbs, Ming Jer Tsai, James R. Lupski, Huda Y. ZoghbiFrans P.M. Cremers, Bert B.A. De Vries, Christian P. Schaaf

Research output: Contribution to journalArticlepeer-review

90 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)303-309
Number of pages7
JournalAmerican Journal of Human Genetics
Issue number2
StatePublished - Feb 6 2014
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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