RESUMO
Gene mapping of inherited ophthalmic diseases such as congenital cataracts, retinal degeneration, glaucoma, age-related macular degeneration, myopia, optic atrophy, and eye malformations has shed more light on the disease pathology, identified targets for research on therapeutics, earlier detection, and treatment options for disease management and patient care. This article details the different approaches to gene identification for both Mendelian and complex eye disorders.
Assuntos
Mapeamento Cromossômico/métodos , Oftalmopatias Hereditárias/genética , Animais , Animais Geneticamente Modificados , Modelos Animais de Doenças , Ligação Genética , Humanos , Polimorfismo de Nucleotídeo Único/genética , Análise de Sequência de DNA/métodosRESUMO
BACKGROUND: Retinoblastoma is the most common intraocular malignancy of childhood. There is a paucity of genetic testing and prenatal genetic diagnosis from India, which has the highest incidence worldwide. MATERIALS AND METHODS: RB1 gene screening of an 8-month-old female child with bilateral retinoblastoma was accomplished using next generation sequencing. The results were used for prenatal testing in this family. RESULTS: A heterozygous germline mutation (chr13: 48951119delA; c.1281delA) was detected, which resulted in premature termination of a protein product (p.Glu428Argfs*29). Prenatal testing in maternal DNA revealed carrier status of the mother. Further clinical examination in the family members revealed retinocytomas in both eyes of the mother and maternal grandmother. Prenatal genetic testing of the developing fetus showed positivity for the mutation. As the family preferred to continue the pregnancy, serial 3-D ultrasounds were carried out every 2 weeks in the third trimester. Ten days after delivery, small extrafoveal tumors developed in both eyes, which were then treated successfully with transpupillary thermotherapy. CONCLUSION: We report the significance of genetic testing in the early detection and management of retinoblastoma from India.
Assuntos
Genes do Retinoblastoma , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Diagnóstico Pré-Natal , Neoplasias da Retina/genética , Proteínas de Ligação a Retinoblastoma/genética , Retinoblastoma/genética , Ubiquitina-Proteína Ligases/genética , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/uso terapêutico , Análise Mutacional de DNA , Etoposídeo/uso terapêutico , Éxons/genética , Feminino , Testes Genéticos , Humanos , Índia , Lactente , Linhagem , Terapia com Prótons , Neoplasias da Retina/diagnóstico , Retinoblastoma/diagnóstico , Vincristina/uso terapêuticoRESUMO
PURPOSE: The aim of this study was to evaluate the use of vascular morphology, around and within the B-mode region of abnormality, for improving the diagnostic accuracy of two of the most common solid breast pathologies. MATERIALS AND METHODS: The B-mode and Doppler images of 117 breast cancers and 366 fibroadenomas and lesions with a fibroadenoma-like appearance were reviewed retrospectively and the morphology of the vascular pattern was evaluated. The ratio of external to internal color Doppler, the external vascular pattern and the connecting vessels to internal vessels were assessed and differentiated into benign and malignant vascular patterns. These patterns were correlated with the histological diagnosis. RESULTS: Vascularity was demonstrated in 95 % of cancers and in 46 % of benign lesions with a trend to increasing vascularity in cancers. This provided poor specificity for excluding cancer in fibroadenomas. Variations in vascular pattern were recorded. The observed benign vascular patterns were avascularity, vascularity in the periphery and peripheral marginal vessels connecting with internal vascularity. The observed malignant vascular patterns were radially aligned external vessels with internal vessels being more numerous than external vessels which connected to radial vessels. (Fisher exact test p < 0.0001). Analysis of the vascular morphology improved the sensitivity for identifying cancers from 97 % (B-mode) to 99 % (B-mode and color Doppler) with a minimal reduction in specificity (93.7 to 92.6 %) or accuracy (94.6 to 94.2 %). CONCLUSION: The presence of vascularity within a lesion, by itself, is no longer a good predictor of malignancy because of the increase in Doppler sensitivity associated with improvements in ultrasound technology. The color Doppler ultrasound vascular pattern morphology improves the accuracy and sensitivity of B-mode image diagnosis, breast cancers and fibroadenomas with a minimal loss of specificity. Any breast lesion with radial rather than marginal connecting vessels should be regarded with suspicion.
