Phenotypic expression variability in Best Disease: a purpose of a series of cases / Variabilidade de expressão Fenotípica na Doença de Best: a propósito de uma série de casos

Abstract The objective of the following work is to document the phenotypic expression variability in Best Disease in first-degree relatives. The information was collected by assessing medical notes, interviewing the patient and obtaining photographic record of the diagnostic methods to which the patient was submitted. Data was analyzed along with a thorough review of the literature. A series of cases were reported in which the patient presenting the phenotypic characteristics of the disease has first degree relatives without ophthalmic findings during examination, but present an abnormal pattern on the electro-oculogram (EOG). Our article reveals the importance of electrophysiological exams in the diagnosis of Best vitelliform macular dystrophy, including the prevention of its clinical manifestation (autosomal dominant), providing concrete subsidies for genetic counseling.

Resumo O objetivo do presente trabalho é a documentação da variabilidade de expressão fenotípica da Doença de Best em parentes de primeiro grau. As informações foram obtidas por meio de revisão do prontuário, entrevista com o paciente e registro fotográfico dos métodos diagnósticos aos quais os pacientes foram submetidos. Dados foram analisados junto a uma extensa revisão da literatura. Relatamos uma série de casos, no qual o paciente que apresenta as alterações fenotípicas da doença tem familiares de primeiro grau sem alterações ao exame oftalmológico, porém os mesmos apresentam padrão anormal de eletro-oculograma (EOG). O nosso artigo revela a importância dos exames eletrofisiológicos no diagnóstico da distrofia macular viteliforme de Best, inclusive no que se refere à prevenção de sua manifestação clínica (autossômica dominante), fornecendo subsídios concretos para o aconselhamento genético.

Direct conversion of human fibroblasts into retinal pigment epithelium-like cells by defined factors

The generation of functional retinal pigment epithelium (RPE) is of great therapeutic interest to the field of regenerative medicine and may provide possible cures for retinal degenerative diseases, including age-related macular degeneration (AMD). Although RPE cells can be produced from either embryonic stem cells or induced pluripotent stem cells, direct cell reprogramming driven by lineage-determining transcription factors provides an immediate route to their generation. By monitoring a human RPE specific Best1::GFP reporter, we report the conversion of human fibroblasts into RPE lineage using defined sets of transcription factors. We found that Best1::GFP positive cells formed colonies and exhibited morphological and molecular features of early stage RPE cells. Moreover, they were able to obtain pigmentation upon activation of Retinoic acid (RA) and Sonic Hedgehog (SHH) signaling pathways. Our study not only established an ideal platform to investigate the transcriptional network regulating the RPE cell fate determination, but also provided an alternative strategy to generate functional RPE cells that complement the use of pluripotent stem cells for disease modeling, drug screening, and cell therapy of retinal degeneration.

Adult-onset foveomacular dystrophy

Objective@#To describe a case of adult-onset foveomacular vitelliform dystrophy (AOFVD).@*Method@#This is a case report.@*Results@#A 22-year-old female presented with painless blurring of vision and metamorphopsia 3 days prior to consultation. There were 2 similar episodes in the past that spontaneously resolved after 2 to 4 weeks. Visual acuity (VA) was 20/50 in the right eye (OD) and 20/40 in the left (OS), both best corrected to 20/25. Dilated-fundus examination revealed a discrete area of mixed hypoand hyperpigmentation 1 disc diameter over the fovea in OD and a solitary round hypopigmented lesion with a hyperpigmented border 3 to 4 disc diameters on the fovea in OS. Fluorescein angiography (FA) revealed an area of hyperfluorescence surrounded by a rim of hypoflourescence in OD and an area of blocked fluorescence with subtle hyperfluorescence superior to the lesion in OS, both of which did not increase in size and intensity toward the late phases. Optical coherence tomography (OCT) revealed neurosensory detachment in both eyes. Electrooculogram (EOG) was normal with Arden ratio of 0.91. VA returned to 20/25 in both eyes, and repeat fundus photography showed no change in the characteristics of the lesions.@*Conclusion@#Differential diagnosis of a hypopigmented macular lesion in the young with self-limited blurring of vision should include AOFVD. FA, OCT, and EOG can help distinguish AOFVD from Best’s disease or other similar macular conditions.

A novel mutation of the VMD2 gene in a Chinese family with best vitelliform macular dystrophy

<p><b>INTRODUCTION</b>In this paper, we report a novel VMD2 gene mutation in a Chinese family with Best vitelliform macular dystrophy.</p><p><b>MATERIALS AND METHODS</b>Ophthalmologic examination and optical coherence tomography (OCT) were performed in 2 members of this family. Mutational screening was performed by single-strand conformation polymorphism (SSCP) and direct sequencing of PCR-amplified DNA fragments, corresponding to the 11 exons of the gene.</p><p><b>RESULTS</b>Sequence analysis identified a previously unreported C to G change, predicting a Phe-113-Leu substitution. Both the proband and his sister harboured this novel mutation. Each had bilateral vitelliform lesions.</p><p><b>CONCLUSIONS</b>A novel mutation in the VMD2 gene (C427G) was found in Chinese patients with Best vitelliform macular dystrophy.</p>