Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) is a recently described autosomal dominant disorder caused by mutations in the NR2F1 gene. There are presently 28 cases of BBSOAS described in the literature. Its common features include developmental delay, intellectual disability, hypotonia, optic nerve atrophy, attention deficit disorder, autism spectrum disorder, seizures, hearing defects, spasticity, and thinning of the corpus callosum. Here we report two unrelated probands with novel, de novo, missense variants in NR2F1 The first is a 14-yr-old male patient with hypotonia, intellectual disability, optic nerve hypoplasia, delayed bone age, short stature, and altered neurotransmitter levels on cerebrospinal fluid testing. The second is a 5-yr-old female with severe developmental delay, motor and speech delay, and repetitive motion behavior. Whole-exome sequencing identified a novel missense NR2F1 variant in each case, Cys86Phe in the DNA-binding domain in Case 1, and a Leu372Pro in the ligand-binding domain in Case 2. The presence of clinical findings compatible with BBSOAS along with structural analysis at atomic resolution using homology-based molecular modeling and molecular dynamic simulations, support the pathogenicity of these variants for BBSOAS. Short stature, abnormal CNS neurotransmitters, and macrocephaly have not been previously reported for this syndrome and may represent a phenotypic expansion of BBSOAS. A review of published cases along with new evidence from this report support genotype-phenotype correlations for this disorder.
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PMID:Novel NR2F1 variants likely disrupt DNA binding: molecular modeling in two cases, review of published cases, genotype-phenotype correlation, and phenotypic expansion of the Bosch-Boonstra-Schaaf optic atrophy syndrome. 2896 36

Background: Nuclear hormone receptor gene, NR2F1, plays a key role in brain and eye development. Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS, MIM #615772) is an autosomal dominant hereditary disorder caused by mutations in this gene. However, there have been few studies describing fundus and optical coherence tomography findings on BBSOAS. Materials and methods: The patient underwent a detailed clinical evaluation and ophthalmic imaging followed by targeted panel next-generation sequencing analysis. Results: A 7-year-old Korean boy, with a history of delayed development and borderline intellectual functioning, was referred to our clinic for evaluation of low vision. He was born full-term with no perinatal insults. Best-corrected visual acuity was 20/100 in both eyes, and latent nystagmus was noted. Dilated fundus examinations revealed optic atrophy in both eyes, and optical coherence tomography showed diffuse thinning of retinal nerve fiber layers. Targeted panel next-generation sequencing showed novel c.513C>G; p.Tyr171Ter (NM_005654.4) in NR2F1 gene. This stop-gain mutation was predicted to be deleterious by in silico prediction programs, and was absent in the current population genomic database. Conclusions: We highlighted the value of genetic testing in definite diagnosis of BBSOAS in patients with unexplained optic atrophy.
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PMID:Targeted panel sequencing identifies a novel NR2F1 mutations in a patient with Bosch-Boonstra-Schaaf optic atrophy syndrome. 3139 1

Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) has been described as an autosomal-dominant disorder caused by mutations in the NR2F1 gene, whose common characteristics include developmental delay, intellectual disability, optic nerve atrophy, hypotonia, attention deficit disorder, autism spectrum disorder, seizures, hearing defects, spasticity and thinning of the corpus callosum. Missense mutations in NR2F1 have been reported to be the major cause of BBSOAS. A possible genotype-phenotype correlation has been considered with missense mutations affecting the ligand-binding domain of NR2F1 as well as whole-gene deletions of NR2F1 showing a milder phenotype of BBSOAS. Here we report on a patient with a novel frameshift mutation in NR2F1 showing the full spectrum of BBOAS indicating an expanded clinical spectrum and a reconsideration of the observed genotype-phenotype correlation.
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PMID:Novel dominant-negative NR2F1 frameshift mutation and a phenotypic expansion of the Bosch-Boonstra-Schaaf optic atrophy syndrome. 3271 14