NR2F1nuclear receptor subfamily 2 group F member 1
Autism Reports / Total Reports
11 / 29Rare Variants / Common Variants
80 / 1Aliases
NR2F1, BBOAS, BBSOAS, COUP-TFI, EAR-3, EAR3, ERBAL3, NR2F2, SVP44, TCFCOUP1, TFCOUP1Associated Syndromes
Bosch-Boonstra-Schaaf optic atrophy syndrome, Bosch-Boonstra-Schaaf optic atrophy syndrome, DD, Tourette syndromeChromosome Band
5q15Associated Disorders
DD/NDD, ADHD, ID, EPS, ASDRelevance to Autism
One of the six patients with Bosch-Boonstra-Schaaf optic atrophy syndrome described in Bosch et al., 2014 presented with autism spectrum disorder with marked obsessive-compulsive behaviors. Evaluation of the clinical features of 20 individuals with novel pathogenic NR2F1 variants demonstrated that, in addition to visual and cognitive deficits, individuals with BBSOAS manifested hypotonia (75%), seizures (40%), repetitive behavior (40%), autism spectrum disorder (35%), oromotor dysfunction (60%), thinning of the corpus callosum (53%), and hearing defects (20%) (Chen et al., 2016). De novo probably damaging missense variants in NR2F1 have also been observed in two ASD probands: one from the Simons Simplex Collection (Sanders et al., 2012), the other from the Autism Sequencing Consortium (De Rubeis et al., 2014).
Molecular Function
The protein encoded by this gene is a nuclear hormone receptor and transcriptional regulator that binds to 5'-AGGTCA-3' repeats. Heterozygous mutations in this gene are a cause of Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS; OMIM 615722), an autosomal dominant disorder characterized by delayed development, moderate intellectual disability, and optic atrophy (Bosch et al., 2014).
External Links
SFARI Genomic Platforms
Reports related to NR2F1 (29 Reports)
# | Type | Title | Author, Year | Autism Report | Associated Disorders |
---|---|---|---|---|---|
1 | Support | De novo mutations revealed by whole-exome sequencing are strongly associated with autism | Sanders SJ , et al. (2012) | Yes | - |
2 | Primary | NR2F1 mutations cause optic atrophy with intellectual disability | Bosch DG , et al. (2014) | No | ID, ASD |
3 | Support | Synaptic, transcriptional and chromatin genes disrupted in autism | De Rubeis S , et al. (2014) | Yes | - |
4 | Recent Recommendation | The expanding clinical phenotype of Bosch-Boonstra-Schaaf optic atrophy syndrome: 20 new cases and possible genotype-phenotype correlations | Chen CA , et al. (2016) | No | ID, ASD, epilepsy/seizures, ADHD |
5 | Support | Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability | Lelieveld SH et al. (2016) | No | - |
6 | Support | The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies | Redin C , et al. (2016) | No | Multiple congenital anomalies |
7 | Support | Lessons learned from additional research analyses of unsolved clinical exome cases | Eldomery MK , et al. (2017) | Yes | - |
8 | Support | A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology | Vissers LE , et al. (2017) | No | - |
9 | Support | Leveraging blood serotonin as an endophenotype to identify de novo and rare variants involved in autism | Chen R , et al. (2017) | Yes | - |
10 | Support | Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder | Lim ET , et al. (2017) | Yes | - |
11 | Support | The combination of whole-exome sequencing and copy number variation sequencing enables the diagnosis of rare neurological disorders | Jiao Q , et al. (2019) | No | DD, ID |
12 | Support | Increased diagnostic and new genes identification outcome using research reanalysis of singleton exome sequencing | Bruel AL , et al. (2019) | No | - |
13 | Support | Autism risk in offspring can be assessed through quantification of male sperm mosaicism | Breuss MW , et al. (2019) | Yes | - |
14 | Support | Rare genetic susceptibility variants assessment in autism spectrum disorder: detection rate and practical use | Husson T , et al. (2020) | Yes | - |
15 | Recent Recommendation | Phenotypic expansion of Bosch-Boonstra-Schaaf optic atrophy syndrome and further evidence for genotype-phenotype correlations | Rech ME et al. (2020) | No | ASD or autistic features, ADHD |
16 | Recent Recommendation | Imbalance of Excitatory/Inhibitory Neuron Differentiation in Neurodevelopmental Disorders with an NR2F1 Point Mutation | Zhang K et al. (2020) | Yes | - |
17 | Support | Missense NR2F1 variant in monozygotic twins affected with the Bosch-Boonstra-Schaaf optic atrophy syndrome | Mio C et al. (2020) | No | - |
18 | Support | NR2F1 regulates regional progenitor dynamics in the mouse neocortex and cortical gyrification in BBSOAS patients | Bertacchi M et al. (2020) | No | - |
19 | Support | Novel dominant-negative NR2F1 frameshift mutation and a phenotypic expansion of the Bosch-Boonstra-Schaaf optic atrophy syndrome | Walsh S et al. (2020) | No | ASD, DD, epilepsy/seizures |
20 | Recent Recommendation | - | Jurkute N et al. (2021) | No | ASD, ADHD, learning disability, epilepsy/seizures |
21 | Support | - | Billiet B et al. (2021) | No | - |
22 | Support | - | Zhou X et al. (2022) | Yes | - |
23 | Positive Association | - | Tsetsos F et al. (2023) | No | - |
24 | Support | - | Yuan B et al. (2023) | Yes | - |
25 | Support | - | Spataro N et al. (2023) | No | - |
26 | Support | - | Bonzano S et al. (2023) | No | - |
27 | Support | - | Jean Christophe Deloulme et al. (2024) | No | - |
28 | Support | - | Ruohao Wu et al. (2024) | Yes | - |
29 | Support | - | Axel Schmidt et al. (2024) | No | - |
Rare Variants (80)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
- | - | copy_number_loss | Unknown | - | - | 32275123 | Rech ME et al. (2020) | |
- | - | copy_number_loss | De novo | - | - | 26986877 | Chen CA , et al. (2016) | |
- | - | copy_number_loss | Unknown | - | - | 26986877 | Chen CA , et al. (2016) | |
- | - | copy_number_loss | De novo | - | - | 24462372 | Bosch DG , et al. (2014) | |
- | - | copy_number_loss | Unknown | - | - | 24462372 | Bosch DG , et al. (2014) | |
- | - | copy_number_loss | De novo | - | - | 34466801 | Jurkute N et al. (2021) | |
- | - | copy_number_loss | Familial | Maternal | - | 32275123 | Rech ME et al. (2020) | |
- | - | complex_structural_alteration | De novo | - | - | 27841880 | Redin C , et al. (2016) | |
c.1117C>T | p.Arg373Ter | stop_gained | De novo | - | - | 32275123 | Rech ME et al. (2020) | |
c.115G>T | p.Glu39Ter | stop_gained | De novo | - | - | 34466801 | Jurkute N et al. (2021) | |
c.353T>G | p.Leu118Ter | stop_gained | De novo | - | - | 34466801 | Jurkute N et al. (2021) | |
c.513G>C | p.Tyr171Ter | stop_gained | Unknown | - | - | 34466801 | Jurkute N et al. (2021) | |
c.698G>A | p.Trp233Ter | stop_gained | De novo | - | - | 34466801 | Jurkute N et al. (2021) | |
- | - | copy_number_loss | Familial | Paternal | Simplex | 26986877 | Chen CA , et al. (2016) | |
c.1198G>T | p.Glu400Ter | stop_gained | De novo | - | - | 34466801 | Jurkute N et al. (2021) | |
c.766T>G | p.Trp256Gly | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.256T>C | p.Cys86Arg | missense_variant | De novo | - | - | 32275123 | Rech ME et al. (2020) | |
c.262G>A | p.Val88Met | missense_variant | De novo | - | - | 32275123 | Rech ME et al. (2020) | |
c.284G>T | p.Gly95Val | missense_variant | Unknown | - | - | 32275123 | Rech ME et al. (2020) | |
c.290A>C | p.His97Pro | missense_variant | Unknown | - | - | 32275123 | Rech ME et al. (2020) | |
c.293A>G | p.Tyr98Cys | missense_variant | De novo | - | - | 32275123 | Rech ME et al. (2020) | |
c.124C>T | p.Gln42Ter | stop_gained | De novo | - | Simplex | 35982159 | Zhou X et al. (2022) | |
c.311A>G | p.Glu104Gly | missense_variant | De novo | - | - | 32275123 | Rech ME et al. (2020) | |
c.323G>T | p.Ser108Ile | missense_variant | Unknown | - | - | 32275123 | Rech ME et al. (2020) | |
c.365G>C | p.Cys122Ser | missense_variant | Unknown | - | - | 32275123 | Rech ME et al. (2020) | |
c.417A>T | p.Gln139His | missense_variant | De novo | - | - | 32275123 | Rech ME et al. (2020) | |
c.931G>C | p.Ala311Pro | missense_variant | Unknown | - | - | 32275123 | Rech ME et al. (2020) | |
c.954G>C | p.Glu318Asp | missense_variant | De novo | - | - | 32275123 | Rech ME et al. (2020) | |
c.82C>T | p.Gln28Ter | stop_gained | De novo | - | Simplex | 28344757 | Chen R , et al. (2017) | |
c.993C>T | p.Asp331%3D | synonymous_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.1217T>C | p.Met406Thr | missense_variant | De novo | - | - | 32275123 | Rech ME et al. (2020) | |
c.2T>C | p.Met1? | initiator_codon_variant | De novo | - | - | 30945278 | Jiao Q , et al. (2019) | |
c.1A>G | p.Met1? | initiator_codon_variant | De novo | - | - | 32275123 | Rech ME et al. (2020) | |
c.2T>C | p.Met1? | initiator_codon_variant | De novo | - | - | 32275123 | Rech ME et al. (2020) | |
c.382T>C | p.Cys128Arg | missense_variant | De novo | - | - | 26986877 | Chen CA , et al. (2016) | |
c.403C>A | p.Arg135Ser | missense_variant | De novo | - | - | 26986877 | Chen CA , et al. (2016) | |
c.413G>A | p.Cys138Tyr | missense_variant | De novo | - | - | 26986877 | Chen CA , et al. (2016) | |
c.425G>T | p.Arg142Leu | missense_variant | De novo | - | - | 26986877 | Chen CA , et al. (2016) | |
c.436T>C | p.Cys146Arg | missense_variant | De novo | - | - | 26986877 | Chen CA , et al. (2016) | |
c.463G>A | p.Ala155Thr | missense_variant | De novo | - | - | 26986877 | Chen CA , et al. (2016) | |
c.289C>T | p.His97Tyr | missense_variant | De novo | - | - | 31231135 | Bruel AL , et al. (2019) | |
c.290A>C | p.His97Pro | missense_variant | De novo | - | - | 34466801 | Jurkute N et al. (2021) | |
c.1103G>A | p.Gly368Asp | missense_variant | De novo | - | - | 26986877 | Chen CA , et al. (2016) | |
c.2T>G | p.Met1? | initiator_codon_variant | De novo | - | - | 26986877 | Chen CA , et al. (2016) | |
c.339C>A | p.Ser113Arg | missense_variant | De novo | - | - | 24462372 | Bosch DG , et al. (2014) | |
c.344G>C | p.Arg115Pro | missense_variant | De novo | - | - | 24462372 | Bosch DG , et al. (2014) | |
c.755T>C | p.Leu252Pro | missense_variant | De novo | - | - | 24462372 | Bosch DG , et al. (2014) | |
c.366C>G | p.Cys122Trp | missense_variant | De novo | - | - | 34466801 | Jurkute N et al. (2021) | |
c.463G>A | p.Ala155Thr | missense_variant | De novo | - | - | 34466801 | Jurkute N et al. (2021) | |
c.599C>G | p.Thr200Arg | missense_variant | De novo | - | - | 34466801 | Jurkute N et al. (2021) | |
c.320A>G | p.Lys107Arg | missense_variant | De novo | - | - | 36980980 | Spataro N et al. (2023) | |
c.1024G>A | p.Glu342Lys | missense_variant | De novo | - | - | 34466801 | Jurkute N et al. (2021) | |
c.1183G>A | p.Gly395Ser | missense_variant | De novo | - | - | 34466801 | Jurkute N et al. (2021) | |
c.403C>T | p.Arg135Cys | missense_variant | De novo | - | - | 31873310 | Breuss MW , et al. (2019) | |
c.91_93dup | p.Arg31dup | inframe_insertion | Unknown | - | - | 34466801 | Jurkute N et al. (2021) | |
c.359dup | p.Tyr120Ter | frameshift_variant | Unknown | - | - | 34466801 | Jurkute N et al. (2021) | |
c.314G>A | p.Gly105Asp | missense_variant | De novo | - | - | 28333917 | Vissers LE , et al. (2017) | |
c.1036_1038del | p.Glu346del | inframe_deletion | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.328_330del | p.Phe110del | inframe_deletion | De novo | - | - | 26986877 | Chen CA , et al. (2016) | |
c.305C>T | p.Thr102Ile | missense_variant | De novo | - | - | 25363760 | De Rubeis S , et al. (2014) | |
c.314G>A | p.Gly105Asp | missense_variant | De novo | - | - | 27479843 | Lelieveld SH et al. (2016) | |
c.327C>A | p.Phe109Leu | missense_variant | De novo | - | - | 39039281 | Axel Schmidt et al. (2024) | |
c.4del | p.Ala2GlnfsTer3 | frameshift_variant | De novo | - | - | 34466801 | Jurkute N et al. (2021) | |
c.531C>G | p.Asp177Glu | missense_variant | De novo | - | Simplex | 28714951 | Lim ET , et al. (2017) | |
c.21_43del | p.Trp8GlyfsTer381 | frameshift_variant | De novo | - | - | 36881370 | Yuan B et al. (2023) | |
c.291del | p.Tyr98ThrfsTer21 | frameshift_variant | De novo | - | - | 26986877 | Chen CA , et al. (2016) | |
c.335G>A | p.Arg112Lys | missense_variant | De novo | - | Simplex | 24462372 | Bosch DG , et al. (2014) | |
c.332A>G | p.Lys111Arg | missense_variant | De novo | - | Simplex | 38764027 | Ruohao Wu et al. (2024) | |
c.380dup | p.Asn127LysfsTer270 | frameshift_variant | Unknown | - | - | 32275123 | Rech ME et al. (2020) | |
c.1184G>C | p.Gly395Ala | missense_variant | De novo | - | Simplex | 32094338 | Husson T , et al. (2020) | |
c.1211G>A | p.Arg404His | missense_variant | De novo | - | Simplex | 22495306 | Sanders SJ , et al. (2012) | |
c.413G>A | p.Cys138Tyr | missense_variant | De novo | - | Simplex | 28327206 | Eldomery MK , et al. (2017) | |
c.51_69dup | p.Asn24GlyfsTer379 | frameshift_variant | Unknown | - | - | 34466801 | Jurkute N et al. (2021) | |
c.2_4delinsGGA | p.MetAla1_?2 | initiator_codon_variant | De novo | - | - | 26986877 | Chen CA , et al. (2016) | |
c.1036_1047del | p.Glu346_Gln349del | inframe_deletion | Unknown | - | - | 34466801 | Jurkute N et al. (2021) | |
c.1083del | p.Asn362ThrfsTer33 | frameshift_variant | De novo | - | Simplex | 32712214 | Walsh S et al. (2020) | |
c.1115T>C | p.Leu372Pro | missense_variant | Familial | Maternal | Multiplex | 34466801 | Jurkute N et al. (2021) | |
c.103_113delinsCGCCGCCGC | p.Gly35ArgfsTer361 | frameshift_variant | De novo | - | - | 26986877 | Chen CA , et al. (2016) | |
c.313G>A | p.Gly105Ser | missense_variant | De novo | - | Multiplex (monozygotic twins) | 32412696 | Mio C et al. (2020) | |
c.1118_1123del | p.Arg373_Leu374del | inframe_deletion | Familial | Maternal | Simplex | 34466801 | Jurkute N et al. (2021) |
Common Variants (1)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Paternal Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
T>A | - | intergenic_variant | - | - | - | 36738982 | Tsetsos F et al. (2023) |
SFARI Gene score
Strong Candidate, Syndromic
Heterozygous mutations in this gene are a cause of Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS; OMIM 615722), an autosomal dominant disorder characterized by delayed development, moderate intellectual disability, and optic atrophy (Bosch et al., 2014). One of the six patients with Bosch-Boonstra-Schaaf optic atrophy syndrome described in Bosch et al., 2014 presented with autism spectrum disorder with marked obsessive-compulsive behaviors. Evaluation of the clinical features of 20 individuals with novel pathogenic NR2F1 variants demonstrated that, in addition to visual and cognitive deficits, individuals with BBSOAS manifested hypotonia (75%), seizures (40%), repetitive behavior (40%), autism spectrum disorder (35%), oromotor dysfunction (60%), thinning of the corpus callosum (53%), and hearing defects (20%) (Chen et al., 2016). De novo probably damaging missense variants in NR2F1 have also been observed in two ASD probands: one from the Simons Simplex Collection (Sanders et al., 2012), the other from the Autism Sequencing Consortium (De Rubeis et al., 2014).
Score Delta: Score remained at 2S
criteria met
See SFARI Gene'scoring criteriaWe considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.
The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."
4/1/2022
Decreased from 3S to 2S
Description
Heterozygous mutations in this gene are a cause of Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS; OMIM 615722), an autosomal dominant disorder characterized by delayed development, moderate intellectual disability, and optic atrophy (Bosch et al., 2014). One of the six patients with Bosch-Boonstra-Schaaf optic atrophy syndrome described in Bosch et al., 2014 presented with autism spectrum disorder with marked obsessive-compulsive behaviors. Evaluation of the clinical features of 20 individuals with novel pathogenic NR2F1 variants demonstrated that, in addition to visual and cognitive deficits, individuals with BBSOAS manifested hypotonia (75%), seizures (40%), repetitive behavior (40%), autism spectrum disorder (35%), oromotor dysfunction (60%), thinning of the corpus callosum (53%), and hearing defects (20%) (Chen et al., 2016). De novo probably damaging missense variants in NR2F1 have also been observed in two ASD probands: one from the Simons Simplex Collection (Sanders et al., 2012), the other from the Autism Sequencing Consortium (De Rubeis et al., 2014).
7/1/2020
Decreased from 3S to 3S
Description
Heterozygous mutations in this gene are a cause of Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS; OMIM 615722), an autosomal dominant disorder characterized by delayed development, moderate intellectual disability, and optic atrophy (Bosch et al., 2014). One of the six patients with Bosch-Boonstra-Schaaf optic atrophy syndrome described in Bosch et al., 2014 presented with autism spectrum disorder with marked obsessive-compulsive behaviors. Evaluation of the clinical features of 20 individuals with novel pathogenic NR2F1 variants demonstrated that, in addition to visual and cognitive deficits, individuals with BBSOAS manifested hypotonia (75%), seizures (40%), repetitive behavior (40%), autism spectrum disorder (35%), oromotor dysfunction (60%), thinning of the corpus callosum (53%), and hearing defects (20%) (Chen et al., 2016). De novo probably damaging missense variants in NR2F1 have also been observed in two ASD probands: one from the Simons Simplex Collection (Sanders et al., 2012), the other from the Autism Sequencing Consortium (De Rubeis et al., 2014).
4/1/2020
Decreased from 3S to 3S
Description
Heterozygous mutations in this gene are a cause of Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS; OMIM 615722), an autosomal dominant disorder characterized by delayed development, moderate intellectual disability, and optic atrophy (Bosch et al., 2014). One of the six patients with Bosch-Boonstra-Schaaf optic atrophy syndrome described in Bosch et al., 2014 presented with autism spectrum disorder with marked obsessive-compulsive behaviors. Evaluation of the clinical features of 20 individuals with novel pathogenic NR2F1 variants demonstrated that, in addition to visual and cognitive deficits, individuals with BBSOAS manifested hypotonia (75%), seizures (40%), repetitive behavior (40%), autism spectrum disorder (35%), oromotor dysfunction (60%), thinning of the corpus callosum (53%), and hearing defects (20%) (Chen et al., 2016). De novo probably damaging missense variants in NR2F1 have also been observed in two ASD probands: one from the Simons Simplex Collection (Sanders et al., 2012), the other from the Autism Sequencing Consortium (De Rubeis et al., 2014).
Reports Added
[Phenotypic expansion of Bosch-Boonstra-Schaaf optic atrophy syndrome and further evidence for genotype-phenotype correlations2020] [Imbalance of Excitatory/Inhibitory Neuron Differentiation in Neurodevelopmental Disorders with an NR2F1 Point Mutation2020] [Missense NR2F1 variant in monozygotic twins affected with the Bosch-Boonstra-Schaaf optic atrophy syndrome2020] [NR2F1 regulates regional progenitor dynamics in the mouse neocortex and cortical gyrification in BBSOAS patients2020]1/1/2020
Decreased from 3S to 3S
Description
Heterozygous mutations in this gene are a cause of Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS; OMIM 615722), an autosomal dominant disorder characterized by delayed development, moderate intellectual disability, and optic atrophy (Bosch et al., 2014). One of the six patients with Bosch-Boonstra-Schaaf optic atrophy syndrome described in Bosch et al., 2014 presented with autism spectrum disorder with marked obsessive-compulsive behaviors. Evaluation of the clinical features of 20 individuals with novel pathogenic NR2F1 variants demonstrated that, in addition to visual and cognitive deficits, individuals with BBSOAS manifested hypotonia (75%), seizures (40%), repetitive behavior (40%), autism spectrum disorder (35%), oromotor dysfunction (60%), thinning of the corpus callosum (53%), and hearing defects (20%) (Chen et al., 2016). De novo probably damaging missense variants in NR2F1 have also been observed in two ASD probands: one from the Simons Simplex Collection (Sanders et al., 2012), the other from the Autism Sequencing Consortium (De Rubeis et al., 2014).
10/1/2019
Decreased from 4S to 3S
New Scoring Scheme
Description
Heterozygous mutations in this gene are a cause of Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS; OMIM 615722), an autosomal dominant disorder characterized by delayed development, moderate intellectual disability, and optic atrophy (Bosch et al., 2014). One of the six patients with Bosch-Boonstra-Schaaf optic atrophy syndrome described in Bosch et al., 2014 presented with autism spectrum disorder with marked obsessive-compulsive behaviors. Evaluation of the clinical features of 20 individuals with novel pathogenic NR2F1 variants demonstrated that, in addition to visual and cognitive deficits, individuals with BBSOAS manifested hypotonia (75%), seizures (40%), repetitive behavior (40%), autism spectrum disorder (35%), oromotor dysfunction (60%), thinning of the corpus callosum (53%), and hearing defects (20%) (Chen et al., 2016). De novo probably damaging missense variants in NR2F1 have also been observed in two ASD probands: one from the Simons Simplex Collection (Sanders et al., 2012), the other from the Autism Sequencing Consortium (De Rubeis et al., 2014).
Reports Added
[New Scoring Scheme]7/1/2019
Decreased from 4S to 4S
Description
Heterozygous mutations in this gene are a cause of Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS; OMIM 615722), an autosomal dominant disorder characterized by delayed development, moderate intellectual disability, and optic atrophy (Bosch et al., 2014). One of the six patients with Bosch-Boonstra-Schaaf optic atrophy syndrome described in Bosch et al., 2014 presented with autism spectrum disorder with marked obsessive-compulsive behaviors. Evaluation of the clinical features of 20 individuals with novel pathogenic NR2F1 variants demonstrated that, in addition to visual and cognitive deficits, individuals with BBSOAS manifested hypotonia (75%), seizures (40%), repetitive behavior (40%), autism spectrum disorder (35%), oromotor dysfunction (60%), thinning of the corpus callosum (53%), and hearing defects (20%) (Chen et al., 2016). De novo probably damaging missense variants in NR2F1 have also been observed in two ASD probands: one from the Simons Simplex Collection (Sanders et al., 2012), the other from the Autism Sequencing Consortium (De Rubeis et al., 2014).
4/1/2019
Decreased from 4S to 4S
Description
Heterozygous mutations in this gene are a cause of Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS; OMIM 615722), an autosomal dominant disorder characterized by delayed development, moderate intellectual disability, and optic atrophy (Bosch et al., 2014). One of the six patients with Bosch-Boonstra-Schaaf optic atrophy syndrome described in Bosch et al., 2014 presented with autism spectrum disorder with marked obsessive-compulsive behaviors. Evaluation of the clinical features of 20 individuals with novel pathogenic NR2F1 variants demonstrated that, in addition to visual and cognitive deficits, individuals with BBSOAS manifested hypotonia (75%), seizures (40%), repetitive behavior (40%), autism spectrum disorder (35%), oromotor dysfunction (60%), thinning of the corpus callosum (53%), and hearing defects (20%) (Chen et al., 2016). De novo probably damaging missense variants in NR2F1 have also been observed in two ASD probands: one from the Simons Simplex Collection (Sanders et al., 2012), the other from the Autism Sequencing Consortium (De Rubeis et al., 2014).
7/1/2017
Decreased from 4S to 4S
Description
Heterozygous mutations in this gene are a cause of Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS; OMIM 615722), an autosomal dominant disorder characterized by delayed development, moderate intellectual disability, and optic atrophy (Bosch et al., 2014). One of the six patients with Bosch-Boonstra-Schaaf optic atrophy syndrome described in Bosch et al., 2014 presented with autism spectrum disorder with marked obsessive-compulsive behaviors. Evaluation of the clinical features of 20 individuals with novel pathogenic NR2F1 variants demonstrated that, in addition to visual and cognitive deficits, individuals with BBSOAS manifested hypotonia (75%), seizures (40%), repetitive behavior (40%), autism spectrum disorder (35%), oromotor dysfunction (60%), thinning of the corpus callosum (53%), and hearing defects (20%) (Chen et al., 2016). De novo probably damaging missense variants in NR2F1 have also been observed in two ASD probands: one from the Simons Simplex Collection (Sanders et al., 2012), the other from the Autism Sequencing Consortium (De Rubeis et al., 2014).
4/1/2017
Decreased from 4S to 4S
Description
Heterozygous mutations in this gene are a cause of Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS; OMIM 615722), an autosomal dominant disorder characterized by delayed development, moderate intellectual disability, and optic atrophy (Bosch et al., 2014). One of the six patients with Bosch-Boonstra-Schaaf optic atrophy syndrome described in Bosch et al., 2014 presented with autism spectrum disorder with marked obsessive-compulsive behaviors. Evaluation of the clinical features of 20 individuals with novel pathogenic NR2F1 variants demonstrated that, in addition to visual and cognitive deficits, individuals with BBSOAS manifested hypotonia (75%), seizures (40%), repetitive behavior (40%), autism spectrum disorder (35%), oromotor dysfunction (60%), thinning of the corpus callosum (53%), and hearing defects (20%) (Chen et al., 2016). De novo probably damaging missense variants in NR2F1 have also been observed in two ASD probands: one from the Simons Simplex Collection (Sanders et al., 2012), the other from the Autism Sequencing Consortium (De Rubeis et al., 2014).
Reports Added
[NR2F1 mutations cause optic atrophy with intellectual disability.2014] [The expanding clinical phenotype of Bosch-Boonstra-Schaaf optic atrophy syndrome: 20 new cases and possible genotype-phenotype correlations.2016] [De novo mutations revealed by whole-exome sequencing are strongly associated with autism.2012] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability2016] [The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies.2016] [Lessons learned from additional research analyses of unsolved clinical exome cases.2017] [Leveraging blood serotonin as an endophenotype to identify de novo and rare variants involved in autism.2017] [A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology.2017]10/1/2016
Decreased from 4S to 4S
Description
Heterozygous mutations in this gene are a cause of Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS; OMIM 615722), an autosomal dominant disorder characterized by delayed development, moderate intellectual disability, and optic atrophy (Bosch et al., 2014). One of the six patients with Bosch-Boonstra-Schaaf optic atrophy syndrome described in Bosch et al., 2014 presented with autism spectrum disorder with marked obsessive-compulsive behaviors. Evaluation of the clinical features of 20 individuals with novel pathogenic NR2F1 variants demonstrated that, in addition to visual and cognitive deficits, individuals with BBSOAS manifested hypotonia (75%), seizures (40%), repetitive behavior (40%), autism spectrum disorder (35%), oromotor dysfunction (60%), thinning of the corpus callosum (53%), and hearing defects (20%) (Chen et al., 2016). De novo probably damaging missense variants in NR2F1 have also been observed in two ASD probands: one from the Simons Simplex Collection (Sanders et al., 2012), the other from the Autism Sequencing Consortium (De Rubeis et al., 2014).
7/1/2016
Decreased from 4S to 4S
Description
Heterozygous mutations in this gene are a cause of Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS; OMIM 615722), an autosomal dominant disorder characterized by delayed development, moderate intellectual disability, and optic atrophy (Bosch et al., 2014). One of the six patients with Bosch-Boonstra-Schaaf optic atrophy syndrome described in Bosch et al., 2014 presented with autism spectrum disorder with marked obsessive-compulsive behaviors. Evaluation of the clinical features of 20 individuals with novel pathogenic NR2F1 variants demonstrated that, in addition to visual and cognitive deficits, individuals with BBSOAS manifested hypotonia (75%), seizures (40%), repetitive behavior (40%), autism spectrum disorder (35%), oromotor dysfunction (60%), thinning of the corpus callosum (53%), and hearing defects (20%) (Chen et al., 2016). De novo probably damaging missense variants in NR2F1 have also been observed in two ASD probands: one from the Simons Simplex Collection (Sanders et al., 2012), the other from the Autism Sequencing Consortium (De Rubeis et al., 2014).
4/1/2016
Increased from to 4S
Description
Heterozygous mutations in this gene are a cause of Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS; OMIM 615722), an autosomal dominant disorder characterized by delayed development, moderate intellectual disability, and optic atrophy (Bosch et al., 2014). One of the six patients with Bosch-Boonstra-Schaaf optic atrophy syndrome described in Bosch et al., 2014 presented with autism spectrum disorder with marked obsessive-compulsive behaviors. Evaluation of the clinical features of 20 individuals with novel pathogenic NR2F1 variants demonstrated that, in addition to visual and cognitive deficits, individuals with BBSOAS manifested hypotonia (75%), seizures (40%), repetitive behavior (40%), autism spectrum disorder (35%), oromotor dysfunction (60%), thinning of the corpus callosum (53%), and hearing defects (20%) (Chen et al., 2016). De novo probably damaging missense variants in NR2F1 have also been observed in two ASD probands: one from the Simons Simplex Collection (Sanders et al., 2012), the other from the Autism Sequencing Consortium (De Rubeis et al., 2014).
Krishnan Probability Score
Score 0.56619311657082
Ranking 1220/25841 scored genes
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Sanders TADA Score
Score 0.40393677506562
Ranking 284/18665 scored genes
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Zhang D Score
Score 0.2346314388017
Ranking 3695/20870 scored genes
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