RESUMO
PURPOSE: Inherited retinal dystrophies (IRDs) and inherited optic neuropathies (IONs) are rare diseases defined by specific clinical and molecular features. The relative prevalence of these conditions was determined in Southern France. METHODS: Patients recruited from a specialized outpatient clinic over a 21-year period underwent extensive clinical investigations and 107 genes were screened by polymerase chain reaction/sequencing. RESULTS: There were 1957 IRD cases (1481 families) distributed in 70% of pigmentary retinopathy cases (56% non-syndromic, 14% syndromic), 20% maculopathies and 7% stationary conditions. Patients with retinitis pigmentosa were the most frequent (47%) followed by Usher syndrome (10.8%). Among non-syndromic pigmentary retinopathy patients, 84% had rod-cone dystrophy, 8% cone-rod dystrophy and 5% Leber congenital amaurosis. Macular dystrophies were encountered in 398 cases (30% had Stargardt disease and 11% had Best disease). There were 184 ION cases (127 families) distributed in 51% with dominant optic neuropathies, 33% with recessive/sporadic forms and 16% with Leber hereditary optic neuropathy. Positive molecular results were obtained in 417/609 families with IRDs (68.5%) and in 27/58 with IONs (46.5%). The sequencing of 5 genes (ABCA4, USH2A, MYO7A, RPGR and PRPH2) provided a positive molecular result in 48% of 417 families with IRDs. Except for autosomal retinitis pigmentosa, in which less than half the families had positive molecular results, about 75% of families with other forms of retinal conditions had a positive molecular diagnosis. CONCLUSIONS: Although gene discovery considerably improved molecular diagnosis in many subgroups of IRDs and IONs, retinitis pigmentosa, accounting for almost half of IRDs, remains only partly molecularly defined.
Assuntos
Oftalmopatias Hereditárias/epidemiologia , Doenças do Nervo Óptico/epidemiologia , Distrofias Retinianas/epidemiologia , Transportadores de Cassetes de Ligação de ATP/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Análise Mutacional de DNA , Proteínas da Matriz Extracelular/genética , Oftalmopatias Hereditárias/diagnóstico , Oftalmopatias Hereditárias/genética , Proteínas do Olho/genética , Feminino , França/epidemiologia , Humanos , Lactente , Proteínas de Filamentos Intermediários/genética , Masculino , Glicoproteínas de Membrana/genética , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular , Mutação , Miosina VIIa , Miosinas/genética , Proteínas do Tecido Nervoso/genética , Doenças do Nervo Óptico/diagnóstico , Doenças do Nervo Óptico/genética , Periferinas , Reação em Cadeia da Polimerase , Distrofias Retinianas/diagnóstico , Distrofias Retinianas/genética , Adulto JovemRESUMO
The aim of this work was to analyse genetic influences on ocular refractive value and axial length using the hypothesis of a polygenic control. The genealogical records of 55 families were used in the analyses. The cohort included 723 individuals and clinical data were collected for 445 individuals with a mean age of 37.86 years. Ocular refraction was determined by standard autorefractometry. Axial length was evaluated by scan ultrasonography. Gender, age and ethnic origin were included as covariates in the statistical analyses. Using variance component analysis via a Markov Chain Monte Carlo (MCMC) method, we estimated the heritability of refractive value and axial length in the pedigree. We then performed a segregation analysis, using Loki, a (MCMC) linkage analysis program for multilocus inheritance models, examining different inheritance models with polygenic components. Polygenic control was modelled under an additive infinitesimal model (which assumes infinite loci with small effects, with additive actions) and under a finite locus model (i.e. several causal loci). The estimates of heritability were 0.20 (95% confidence interval (CI) 0.04-0.36) for refractive value and 0.20 (95% CI 0.03-0.43) for axial length. Segregation analyses suggested that ocular refraction and axial length are under a polygenic control. A finite number of genes were identified with or without a polygenic, infinitesimal component. Ocular refraction is mildly-moderately heritable in the studied population.