A novel mutation in the NR2E3 gene associated with Goldmann-Favre syndrome and vasoproliferative tumor of the retina.
Mol Vis
; 20: 724-31, 2014.
Article
em En
| MEDLINE
| ID: mdl-24891813
ABSTRACT
PURPOSE:
Various autosomal recessive retinal dystrophies are reported to be associated with mutations in nuclear receptor subfamily 2, group E, member 3 (NR2E3, also called PNR) gene. The present study proposed to understand the clinical and genetic characteristics of the family of a patient with an ocular phenotype consistent with Goldmann-Favre syndrome (GFS) and vasoproliferative tumors of the retina (VPTRs).METHODS:
Twelve family members of the proband from three generations underwent complete ophthalmic examination, including best-corrected visual acuity with Snellen optotypes, tonometry, biomicroscopic examination, indirect ophthalmoscopy after pupillary dilatation, computerized perimetry, optical coherence tomography, fundus photography, intravenous fluorescein angiography, and electroretinography (ERG). All the study subjects underwent genetic analysis of the entire coding region of the NR2E3 gene with the bidirectional DNA sequencing approach. Hundred healthy individuals were screened for the variant.RESULTS:
The phenotype of the proband had features of GFS with VPTRs. The tumors showed complete resolution with cryotherapy and transpupillary thermotherapy (TTT). Sequencing of the entire coding region of the NR2E3 gene in the proband revealed a novel homozygous c.1117 A>G variant that led to the amino acid change from aspartic acid to glycine at position 406 (p.D406G). This change was present in the homozygous state in affected family members and in the heterozygous state in unaffected family members, and was undetectable in the control subjects. The identified novel p.D406G homozygous mutation was at an evolutionarily highly conserved region and may possibly affect the protein function (Sorting Intolerant From Tolerant [SIFT] score = 0.00).CONCLUSIONS:
Patients with GFS may present with retinal VPTRs that respond to therapy with cryotherapy and TTT. Molecular genetic studies helped to identify a novel p.D406G mutation in the affected members, which will aid in confirming the diagnosis, for genetic counseling of family members and potentially provide some form of therapy for the affected patients.
Texto completo:
1
Coleções:
01-internacional
Temas:
Cuidados_paliativos
/
Geral
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Tipos_de_cancer
/
Outros_tipos
Base de dados:
MEDLINE
Assunto principal:
Degeneração Retiniana
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Transtornos da Visão
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Oftalmopatias Hereditárias
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Neoplasias da Retina
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Predisposição Genética para Doença
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Receptores Nucleares Órfãos
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Estudos de Associação Genética
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Mutação
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Male
Idioma:
En
Revista:
Mol Vis
Assunto da revista:
BIOLOGIA MOLECULAR
/
OFTALMOLOGIA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Índia