TY - JOUR
T1 - NR2F1 mutations cause optic atrophy with intellectual disability
AU - Bosch, Daniëlle G.M.
AU - Boonstra, F. Nienke
AU - Gonzaga-Jauregui, Claudia
AU - Xu, Mafei
AU - De Ligt, Joep
AU - Jhangiani, Shalini
AU - Wiszniewski, Wojciech
AU - Muzny, Donna M.
AU - Yntema, Helger G.
AU - Pfundt, Rolph
AU - Vissers, Lisenka E.L.M.
AU - Spruijt, Liesbeth
AU - Blokland, Ellen A.W.
AU - Chen, Chun An
AU - Lewis, Richard A.
AU - Tsai, Sophia Y.
AU - Gibbs, Richard A.
AU - Tsai, Ming Jer
AU - Lupski, James R.
AU - Zoghbi, Huda Y.
AU - Cremers, Frans P.M.
AU - De Vries, Bert B.A.
AU - Schaaf, Christian P.
N1 - Funding Information:
We are grateful to the individuals involved and their families for their support and cooperation. This work has been supported by grants from Stichting ODAS that contributed through UitZicht (to F.N.B. and F.P.M.C.), Vereniging Bartiméus-Sonneheerdt (5781251 to F.N.B. and F.P.M.C.), and the Netherlands Organisation for Health Research and Development (ZON-MW grant 917-86-319 to B.B.A.d.V). Additionally, this study was accomplished in part through the Center for Mendelian Genomics research effort funded by The National Institutes of Health (NIH) and supported by the National Human Genome Research Institute grant U54HG006542 to the Baylor-Hopkins Center for Mendelian Genomics. C.P.S. is a recipient of a Clinical Scientist Development Award by the Doris Duke Charitable Foundation. His work is generously supported by the Stanford and Joan Alexander Family. M.-J.T. and S.Y.T. are supported by NIH grants (DK45641 and HL114539). W.W. is supported by a K23NS078056 grant from the NINDS. R.A.L. is a Senior Scientific Investigator of Research to Prevent Blindness, New York.
PY - 2014/2/6
Y1 - 2014/2/6
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ajhg.2014.01.002
DO - 10.1016/j.ajhg.2014.01.002
M3 - Article
C2 - 24462372
AN - SCOPUS:84893770103
SN - 0002-9297
VL - 94
SP - 303
EP - 309
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 2
ER -