RESUMEN
Retinitis pigmentosa (RP), the most frequent form of inherited retinal dystrophy is characterized by progressive photoreceptor degeneration. Many genes have been implicated in RP development, but several others remain to be identified. Using a combination of homozygosity mapping, whole-exome and targeted next-generation sequencing, we found a novel homozygous nonsense mutation in SAMD11 in five individuals diagnosed with adult-onset RP from two unrelated consanguineous Spanish families. SAMD11 is ortholog to the mouse major retinal SAM domain (mr-s) protein that is implicated in CRX-mediated transcriptional regulation in the retina. Accordingly, protein-protein network analysis revealed a significant interaction of SAMD11 with CRX. Immunoblotting analysis confirmed strong expression of SAMD11 in human retina. Immunolocalization studies revealed SAMD11 was detected in the three nuclear layers of the human retina and interestingly differential expression between cone and rod photoreceptors was observed. Our study strongly implicates SAMD11 as novel cause of RP playing an important role in the pathogenesis of human degeneration of photoreceptors.
Asunto(s)
Proteínas del Ojo/metabolismo , Proteínas de Homeodominio/metabolismo , Distrofias Retinianas/genética , Retinitis Pigmentosa/genética , Transactivadores/metabolismo , Anciano , Animales , Proteínas Co-Represoras/metabolismo , Codón sin Sentido , Estudios de Cohortes , Hibridación Genómica Comparativa , Consanguinidad , Análisis Mutacional de ADN , Exoma , Femenino , Regulación de la Expresión Génica , Genes Recesivos , Homocigoto , Humanos , Masculino , Ratones , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Mapeo de Interacción de Proteínas , Retina/metabolismo , Retina/fisiopatología , Distrofias Retinianas/etiología , Distrofias Retinianas/metabolismo , Células Fotorreceptoras Retinianas Bastones/metabolismo , Retinitis Pigmentosa/etiología , Retinitis Pigmentosa/metabolismo , España , Factores de Transcripción/metabolismoRESUMEN
OBJECTIVES: To establish the prevalence and severity of diabetic retinopathy (DR) in a sample of patients from "Health Area 3" in the Community of Madrid using non-mydriatic retinography and telemedicine. METHODS: All patients who had their ocular fundus examined due to one of the following conditions were included in the sample: type 1 diabetes (DM1), type 2 non- insulin-dependent diabetes (DM2NID), and type 2 insulin-dependent diabetes (DM2ID). In all cases, 3-field retinographies were taken of both eyes to be evaluated for the presence of DR, and its severity, by an ophthalmologist at the hospital. RESULTS: No DR was observed in 79% of the patients examined, 9% had a mild non-proliferative DR, 9% had a moderate non-proliferative DR, and 1% had a severe non-proliferative DR. The estimated prevalence of DR in "Health Area 3" of the Community of Madrid was thus 21%. In 12% of the examinations the retinographies were considered "low quality", thus requiring a second evaluation at hospital. CONCLUSIONS: The use of non-mydriatic retinography and telemedicine is an adequate method for the screening of DR among the diabetic population.
