RESUMO
Purpose: Rare interchange haplotypes in exon 3 of the OPN1LW and OPN1MW opsin genes cause X-linked myopia, color vision defect, and cone dysfunction. The severity of the disease varies on a broad scale from nonsyndromic high myopia to blue cone monochromatism. Here, we describe a new genotype-phenotype correlation attributed to rare exon 3 interchange haplotypes simultaneously present in the long- and middle-wavelength sensitive opsin genes (L- and M-opsin genes). Methods: A multigenerational family with X-linked high myopia and cone dystrophy was investigated. Results: Affected male patients had infantile onset myopia with normal visual acuity and color vision until their forties. Visual acuity decreased thereafter, along with the development of severe protan and deutan color vision defects. A mild decrease in electroretinography response of cone photoreceptors was detected in childhood, which further deteriorated in middle-aged patients. Rods were also affected, however, to a lesser extent than cones. Clinical exome sequencing identified the LVAVA and MVAVA toxic haplotypes in the OPN1LW and OPN1MW opsin genes, respectively. Conclusion: Here, we show that LVAVA haplotype of the OPN1LW gene and MVAVA haplotype of the OPN1MW gene cause apparently nonsyndromic high myopia in young patients but lead to progressive cone-rod dystrophy with deuteranopia and protanopia in middle-aged patients corresponding to a previously unknown disease course. To the best of our knowledge, this is the first report on the joint effect of these toxic haplotypes in the two opsin genes on chromosome X.
Assuntos
Cromossomos Humanos X/genética , Defeitos da Visão Cromática/genética , DNA/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Miopia/genética , Células Fotorreceptoras Retinianas Bastonetes/patologia , Opsinas de Bastonetes/genética , Adolescente , Adulto , Criança , Defeitos da Visão Cromática/diagnóstico , Defeitos da Visão Cromática/metabolismo , Progressão da Doença , Eletrorretinografia , Feminino , Estudos de Associação Genética , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Doenças Genéticas Ligadas ao Cromossomo X/metabolismo , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Miopia/diagnóstico , Miopia/metabolismo , Linhagem , Fenótipo , Reação em Cadeia da Polimerase , Células Fotorreceptoras Retinianas Bastonetes/metabolismo , Opsinas de Bastonetes/metabolismo , Adulto JovemRESUMO
PURPOSE: The study investigated the reproducibility of orbital blood flow measurements with color Doppler imaging (CDI) at different stages of observer experience. METHODS: The subjects were 31 healthy volunteers and 2 sequential groups of 25 glaucoma patients each. Repeated blood flow measurements (usually 3 sets) in orbital vessels (ophthalmic artery, short posterior ciliary arteries, central retinal artery, and central retinal vein) were performed by the same observer in a single session in each subject. RESULTS: The parameters with the best reproducibility were the resistance index (mean coefficient of variation [COV], 3.3-8.8%), the peak systolic velocity (mean COV, 6.9-13.7%), the time-averaged velocity (mean COV, 7.2-16.0%), and the systolic acceleration time (mean COV, 8.8-12.3%). The mean COV was greater (9.9-20.3%) for the other arterial flow parameters (end-diastolic velocity and systolic acceleration) and for the venous flow velocities (maximum and minimum). The COVs of the parameters were improved by 20-40% as the observer became more experienced in ophthalmic CDI. CONCLUSIONS: We confirm the general reliability of CDI measurements in orbital vessels and show that observer experience improves reproducibility. It appears, however, that observer performance in these measurements is vessel specific.