NR2F1 mutations cause optic atrophy with intellectual disability.

TitleNR2F1 mutations cause optic atrophy with intellectual disability.
Publication TypeJournal Article
Year of Publication2014
AuthorsBosch, DGM, F Boonstra, N, Gonzaga-Jauregui, C, Xu, M, de Ligt, J, Jhangiani, S, Wiszniewski, W, Muzny, DM, Yntema, HG, Pfundt, R, Vissers, LELM, Spruijt, L, Blokland, EAW, Chen, C-A, Lewis, RA, Tsai, SY, Gibbs, RA, Tsai, M-J, Lupski, JR, Zoghbi, HY, Cremers, FPM, de Vries, BBA, Schaaf, CP
Corporate Authors
JournalAm J Hum Genet
Volume94
Issue2
Pagination303-9
Date Published2014 Feb 6
ISSN1537-6605
KeywordsAdolescent, Adult, Amino Acid Sequence, Child, Child, Preschool, COUP Transcription Factor I, DNA-Binding Proteins, Female, Genotype, Humans, Intellectual Disability, Male, Molecular Sequence Data, Mutation, Missense, Optic Atrophy, Phenotype, Young Adult, Zinc Fingers
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.

DOI10.1016/j.ajhg.2014.01.002
Alternate JournalAm. J. Hum. Genet.
PubMed ID24462372
PubMed Central IDPMC3928641
Grant ListU54 HG006542 / HG / NHGRI NIH HHS / United States
DK45641 / DK / NIDDK NIH HHS / United States
U54HG006542 / HG / NHGRI NIH HHS / United States
P01 DK059820 / DK / NIDDK NIH HHS / United States
U54 HD083092 / HD / NICHD NIH HHS / United States
R01 DK045641 / DK / NIDDK NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
HL114539 / HL / NHLBI NIH HHS / United States
K23 NS078056 / NS / NINDS NIH HHS / United States
R37 DK045641 / DK / NIDDK NIH HHS / United States
R01 HL114539 / HL / NHLBI NIH HHS / United States
K23NS078056 / NS / NINDS NIH HHS / United States