RESUMO
OBJECTIVES: To describe the clinical phenotype of a novel autosomal recessively inherited vitreoretinal dystrophy in one generation of a family originating from eastern Switzerland. METHODS: A clinical study including electroretinographic investigations followed by laboratory-based genetic and molecular analysis. Four affected and 3 unaffected members of the family were examined. Ten candidate regions were tested by linkage analysis with highly polymorphic molecular markers or with intragenic restriction fragment length polymorphisms. RESULTS: Of 8 siblings,4 were affected, showing high myopia with pronounced vitreous liquefaction, retinitis pigmentosa-like retinal degeneration, diffuse retinal pigment epithelium atrophy, macular staphylomata, and premature cataract formation. Strikingly abnormal results on electroretinograms, affecting both the rod and the cone systems, revealed an extensive defect of retinal function, unlike those usually found in pathologic myopia. No extraocular manifestations were observed. Three types of nonsyndromic high myopia, Stickler syndrome I, II, and III, Wagner syndrome, Knobloch syndrome, Goldmann-Favre dystrophy, and multiple vitreoretinopathies were excluded by linkage analysis. CONCLUSIONS: The reported phenotype as well as the results of molecular linkage analysis in the siblings described here suggest an autosomal recessively inherited vitreoretinal dystrophy, which, to our knowledge, has not been described until now.
Assuntos
Catarata/genética , Oftalmopatias Hereditárias/genética , Genes Recessivos , Miopia/genética , Degeneração Retiniana/genética , Corpo Vítreo/patologia , Idoso , Atrofia , Catarata/diagnóstico , Eletrorretinografia , Oftalmopatias Hereditárias/diagnóstico , Feminino , Ligação Genética , Marcadores Genéticos , Humanos , Masculino , Miopia/diagnóstico , Epitélio Pigmentado Ocular/patologia , Reação em Cadeia da Polimerase , Degeneração Retiniana/diagnóstico , Transtornos da Visão/genética , Testes de Campo Visual , Campos VisuaisRESUMO
OBJECTIVES: To localize the gene that causes an autosomal recessively inherited vitreoretinal dystrophy that has not been described, to our knowledge, and to analyze a candidate gene mapped to 22q13 (fibulin-1 [FBLN1]). METHODS: Homozygosity mapping with 500 microsatellite markers spread over the whole genome (mean distance, 7.2 centimorgans [cM]) and mutation analysis of the complete coding region of FBLN1. RESULTS: Homozygosity for all analyzed markers was found in the 4 affected siblings in a region on chromosome 22 encompassing 12 cM from D22S444 (centromeric) to D22S1170 (telomeric). Lod scores were between 0.017 and 2.36 (theta = 0). A mutation analysis of the complete coding region of FBLN1, which encodes interacting extracellular matrix proteins, revealed 4 previously undescribed single nucleotide polymorphisms. CONCLUSIONS: A genomewide homozygosity mapping analysis supported the hypothesis that the gene responsible for a unique vitreoretinal dystrophy is located on chromosome 22q13. No obviously pathogenic mutation was found in the candidate gene, FBLN1.
Assuntos
Proteínas de Ligação ao Cálcio/genética , Mapeamento Cromossômico , Cromossomos Humanos Par 22/genética , Oftalmopatias Hereditárias/genética , Degeneração Retiniana/genética , Corpo Vítreo/patologia , Idoso , Sequência de Bases , Análise Mutacional de DNA , Proteínas da Matriz Extracelular/genética , Oftalmopatias Hereditárias/patologia , Feminino , Genes Recessivos , Haplótipos , Homozigoto , Humanos , Escore Lod , Masculino , Repetições de Microssatélites , Biologia Molecular , Dados de Sequência Molecular , Linhagem , Polimorfismo de Nucleotídeo Único , Degeneração Retiniana/patologia , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
PURPOSE: To investigate the results of pars plana vitrectomy combined with long-term intraocular tamponade in patients with a stage 2 macular hole. METHODS: In a retrospective study, 50 consecutive eyes operated on for stage 2 macular hole were reviewed. The surgical technique included pars plana vitrectomy, separation of the posterior hyaloid, and intraocular tamponade with either 12.5% perfluropropane (C(3)F(8)) gas or silicone oil. Patients treated with C(3)F(8) were instructed to keep face-down positioning for 3 or 4 weeks. Removal of silicone oil took place 4 or 5 weeks after the vitrectomy. RESULTS: Closure of the macular hole was achieved in all 50 eyes after one operation. The mean postoperative best-corrected distance visual acuity was 20/32 (range, 20/63-20/20), with 49 eyes (98%) having a postoperative visual acuity of 20/50 or better. Visual acuity improved in all eyes postoperatively, with a mean gain of 4.84 +/- 1.95 ETDRS lines. CONCLUSION: For stage 2 macular holes, vitrectomy combined with long-term intraocular tamponade can result in a very favorable anatomic and functional outcome that is as good as or better than the results described for other modalities. This approach simplifies the surgical technique, and both adjuvant-related complications and potential retinal damage related to internal limiting membrane peeling or use of indocyanine green are avoided.