RESUMEN
The authors report a case of a 6-week-old girl with microphthalmia, posterior lenticonus, persistent fetal vasculature, and coloboma of the right eye, with morning glory disc anomaly and falciform retinal folds of the left eye. Genetic testing revealed a previously unreported mutation (c.1471A>G [p.T491A]) in the gene ZNF408, which has been associated with autosomal recessive retinitis pigmentosa and autosomal dominant familial exudative vitreoretinopathy. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:253-256.].
Asunto(s)
Anomalías Múltiples , Coloboma/diagnóstico , Enfermedades de la Córnea/diagnóstico , Proteínas de Unión al ADN/genética , Mutación , Nervio Óptico/anomalías , Síndrome de Circulación Fetal Persistente/diagnóstico , Factores de Transcripción/genética , Coloboma/genética , Córnea/anomalías , Córnea/diagnóstico por imagen , Enfermedades de la Córnea/congénito , Enfermedades de la Córnea/genética , Análisis Mutacional de ADN , Proteínas de Unión al ADN/metabolismo , Anomalías del Ojo , Femenino , Angiografía con Fluoresceína , Fondo de Ojo , Humanos , Lactante , Imagen por Resonancia Magnética , Síndrome de Circulación Fetal Persistente/genética , Factores de Transcripción/metabolismo , Dedos de ZincRESUMEN
MicroRNAs (miRNAs) are released from cells in association with proteins or microvesicles. We previously reported that malignant transformation changes the assortment of released miRNAs by affecting whether a particular miRNA species is released or retained by the cell. How this selectivity occurs is unclear. Here we report that selectively exported miRNAs, whose release is increased in malignant cells, are packaged in structures that are different from those that carry neutrally released miRNAs (n-miRNAs), whose release is not affected by malignancy. By separating breast cancer cell microvesicles, we find that selectively released miRNAs associate with exosomes and nucleosomes. However, n-miRNAs of breast cancer cells associate with unconventional exosomes, which are larger than conventional exosomes and enriched in CD44, a protein relevant to breast cancer metastasis. Based on their large size, we call these vesicles L-exosomes. Contrary to the distribution of miRNAs among different microvesicles of breast cancer cells, normal cells release all measured miRNAs in a single type of vesicle. Our results suggest that malignant transformation alters the pathways through which specific miRNAs are exported from cells. These changes in the particles and their miRNA cargo could be used to detect the presence of malignant cells in the body.