RESUMEN
Familial exudative vitreoretinopathy (FEVR) is an inherited blinding disorder characterized by the abnormal development of the retinal vasculature. The majority of mutations identified in FEVR are found within four genes that encode the receptor complex (FZD4, LRP5, and TSPAN12) and ligand (NDP) of a molecular pathway that controls angiogenesis, the Norrin-ß-catenin signaling pathway. However, half of all FEVR-affected case subjects do not harbor mutations in these genes, indicating that further mutated genes remain to be identified. Here we report the identification of mutations in CTNNB1, the gene encoding ß-catenin, as a cause of FEVR. We describe heterozygous mutations (c.2142_2157dup [p.His720∗] and c.2128C>T [p.Arg710Cys]) in two dominant FEVR-affected families and a de novo mutation (c.1434_1435insC [p.Glu479Argfs∗18]) in a simplex case subject. Previous studies have reported heterozygous de novo CTNNB1 mutations as a cause of syndromic intellectual disability (ID) and autism spectrum disorder, and somatic mutations are linked to many cancers. However, in this study we show that Mendelian inherited CTNNB1 mutations can cause non-syndromic FEVR and that FEVR can be a part of the syndromic ID phenotype, further establishing the role that ß-catenin signaling plays in the development of the retinal vasculature.
Asunto(s)
Enfermedades de la Retina/genética , Transducción de Señal , beta Catenina/metabolismo , Secuencia de Bases , Enfermedades Hereditarias del Ojo , Vitreorretinopatías Exudativas Familiares , Femenino , Heterocigoto , Humanos , Luciferasas/metabolismo , Masculino , Modelos Biológicos , Proteínas Mutantes/metabolismo , Mutación/genética , Linaje , Fenotipo , Transcripción GenéticaRESUMEN
Idiopathic orbital inflammation, also known as orbital pseudotumour, is a term describing a spectrum of idiopathic, non-neoplastic, non-infectious, space-occupying orbital lesion without identifiable local or systemic cause. This disease occurs mainly in young adults and typically presents with acute proptosis, chemosis and limited extraocular movement. Herein an unusual case of idiopathic orbital inflammation presenting with bilateral exudative retinal detachment in a 9-year-old girl is described. It demonstrates that prompt diagnosis and corticosteroid treatment can yield good clinical response and significant visual recovery.
