RESUMEN
PURPOSE: To describe the clinical and genetic characteristics (novel mutation in BEST1 gene) of a Spanish patient with autosomal recessive bestrophinopathy (ARB). METHODS: The detailed ophthalmological examination included best corrected visual acuity (BCVA), color and autofluorescence photography, fluorescein angiography, optical coherence tomography, and electrophysiology tests. A next-generation sequencing (NGS) strategy was applied to the index patient, and then sequenced in an Illumina NextSeq500 system. RESULTS: A 55-year-old male presented with a BCVA of 20/25 in the right eye and 20/20 in the left eye. Fundoscopy revealed perifoveal yellow flecked-like lesions. Fluorescein angiography and fundus autofluorescence results were consistent with pattern dystrophy. A homozygous frameshift mutation in BEST1 (c.341_342del; p.(Leu114Glnfs*57)) was identified as the cause of the disease. CONCLUSION: ARB is a genetic disease that leads to irreversible visual loss. In this report we found a novel mutation responsible for this disease.
Asunto(s)
Electrorretinografía , Enfermedades de la Retina , Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina , Bestrofinas/genética , Canales de Cloruro/genética , Análisis Mutacional de ADN , Electrooculografía , Enfermedades Hereditarias del Ojo , Proteínas del Ojo/genética , Proteínas del Ojo/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Mutación , Linaje , Enfermedades de la Retina/diagnóstico , Enfermedades de la Retina/genética , Enfermedades de la Retina/patología , Tomografía de Coherencia ÓpticaRESUMEN
Mutations in the EYS gene are one of the major causes of autosomal recessive retinitis pigmentosa. EYS-retinopathy presents a severe clinical phenotype, and patients currently have no therapeutic options. The progress in personalised medicine and gene and cell therapies hold promise for treating this degenerative disease. However, lack of understanding and incomplete comprehension of disease's mechanism and the role of EYS in the healthy retina are critical limitations for the translation of current technical advances into real therapeutic possibilities. This review recapitulates the present knowledge about EYS-retinopathies, their clinical presentations and proposed genotype-phenotype correlations. Molecular details of the gene and the protein, mainly based on animal model data, are analysed. The proposed cellular localisation and roles of this large multi-domain protein are detailed. Future therapeutic approaches for EYS-retinopathies are discussed.
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Degeneración Retiniana , Retinitis Pigmentosa , Animales , Análisis Mutacional de ADN , Electrorretinografía , Proteínas del Ojo/genética , Humanos , Mutación/genética , Degeneración Retiniana/genética , Degeneración Retiniana/terapiaRESUMEN
Retinal dystrophies associated to mutations in the CRB1 gene comprise a wide array of clinical presentations. A blood sample from a patient with a family history of CRB1-retinal dystrophy was used to prepare the iPSC line ESi082-A. The genotype of the donor, affected of a perifoveal-bilateral macular dystrophy includes one frameshift deletion and one hypomorphic allele. ESi082-A cell line has been characterized for pluripotency and will be used to prepare retinal cellular models to study the dysfunction leading to the disease.
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Células Madre Pluripotentes Inducidas , Degeneración Macular , Distrofias Retinianas , Proteínas del Ojo/genética , Humanos , Degeneración Macular/genética , Proteínas de la Membrana/genética , Mutación , Proteínas del Tejido Nervioso/genética , Linaje , Fenotipo , Distrofias Retinianas/genéticaRESUMEN
Background: To characterize the phenotype and genotype of a rare syndrome associating posterior microphthalmos (PM), retinitis pigmentosa (RP), and foveoschisis in a consanguineous Spanish family. Methods: The study involved five family members, consisting of three siblings and their parents. All members underwent comprehensive eye examinations for best corrected visual acuity, axial length and refractive error, electroretinography (ERG), fundus photography, retinal fluorescein angiography (FA), and optical coherence tomography (OCT). Clinical exome sequencing of more than 6,000 clinically relevant genes (SureSelect Focused Exome, Agilent) was performed using the Illumina HiSeq 3000 system. Candidate variants were validated and segregated by Sanger sequencing. Results: The affected siblings had bilateral shortening of the posterior ocular segment and normal anterior segment dimensions. The fundoscopy, ERG, and FA results were compatible with RP. Macular OCT analysis revealed schisis of the outer retinal layer. Our data analysis pipeline identified a homozygous frameshift mutation in exon 5 of the membrane frizzled-related protein (MFRP) gene (c.498delC; p.Asn167Thrfs*25). Conclusion: Our study confirmed the association of PM with RP as an autosomal recessive syndrome. Although this has previously been described, it seems that there are some constant (i.e., PM and RP) and some variable features (i.e., optic nerve drusen and foveoschisis). The MFRP mutation has also been detected in other studies associating PM with RP. Analysis of a larger series of cases at the clinical and genetic levels would certainly help us to better understand the phenotype-genotype correlations of this syndrome.
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Fóvea Central/patología , Predisposición Genética a la Enfermedad , Proteínas de la Membrana/genética , Microftalmía/etiología , Mutación , Retinitis Pigmentosa/etiología , Retinosquisis/etiología , Adulto , Niño , Femenino , Fóvea Central/metabolismo , Humanos , Masculino , Microftalmía/patología , Fenotipo , Pronóstico , Retinitis Pigmentosa/patología , Retinosquisis/patología , Adulto JovenRESUMEN
Age-related macular degeneration (AMD) is the leading cause of adult blindness in developed countries and is characterized by progressive degeneration of the macula, the central region of the retina. A human induced pluripotent stem cell (hiPSC) line was derived from peripheral blood mononuclear cells (PBMCs) from a patient with a clinical diagnosis of dry AMD carrying the CFH Y402H polymorphism. Sendai virus was using for reprogramming and the pluripotent and differentiation capacity of the cells were assessed by immunocytochemistry and RT-PCR.
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Técnicas de Reprogramación Celular , Células Madre Pluripotentes Inducidas , Degeneración Macular , Polimorfismo Genético , Anciano de 80 o más Años , Línea Celular , Factor H de Complemento/genética , Factor H de Complemento/metabolismo , Femenino , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes Inducidas/patología , Degeneración Macular/genética , Degeneración Macular/metabolismo , Degeneración Macular/patologíaRESUMEN
Retinitis pigmentosa (RP) is an inherited retinal degenerative disease. Mutations in EYS have been associated with autosomal recessive RP. The human iPS cell line, CABi002-A, derived from peripheral blood mononuclear cells from a patient carrying a heterozygous double mutation in EYS gene was generated by non-integrative reprogramming technology, using hOCT3/4, hSOX2, hc-MYC and hKLF4 reprogramming factors. Pluripotency and differentiation capacity were assessed by immunocytochemistry and RT-PCR. This iPSC line can be further differentiated towards the affected cells to understand the pathophysiology of the disease and test new therapeutic strategies.