Avaliação fenotípica e genotípica de famílias brasileiras com a síndrome de Jalili

Abstract

The Jalili syndrome (JS) is a rare, hereditary disorder characterized by the combination of retinal photoreceptor cell dystrophy, cones and rods (CRD), and imperfect amelogenesis (AI), resulting from mutations in Cyclin and CBS Domain Divalent Metal Cation Transport Mediator 4 (CNNM4). The CNNM4 gene is responsible for the transport of metal ions and a variety of mutations in this gene have been reported in different countries. This study aimed to evaluate the clinical, imaging, genetic and inheritance patterns in two new families affected by JS. All members of two families identified with characteristics suggestive of SJ were studied, being the first family resident in the city of Porteirinha - Minas Gerais, and the second resident in Americana - São Paulo, without relation of kinship of between both families. The members of the two families were submitted to ophthalmological, odontological and genetic evaluations. In the first family, being the heterozygous parents of consanguineous marriage, the JS was caused by the mutation homozygous p.L324P (c.971T> C) missense transition and the affected patient had CRD and AI. In the second family, there was no consanguineous marriage, being the normal mother, father and daughter were affected,a specific combination of a composite heterozygous mutation was found the p.L324P (c.971T> C) missense transition and a new mutation p.Y581* (c.1743C>G), and the daughter showed phenotypic characteristics for CRD and AI, but her father only developed ocular alterations. Together, these findings suggested that the p.L324P mutation in homozygousness induced a complete phenotype with CRD and AI, but in heterozygosis and in composition with the new mutation p.Y581 nonsense* in CNNM4 promoted variable clinical expressiveness, with no manifestation of dental phenotype. These different phenotypes can be explained by deletions affecting the homologous allele, epistasis, or interactions with environmental factors that lead to the residual activity of the protein. These two families characterize the first described cases of JS in Brazil.