Distrofia corneal granular autosómica dominante causada por mutación del gen TGFBI en una familia mexicana

Abstract

RESUMENObjetivo: Las distrofias corneales son un grupo de alteraciones hereditarias en las que una acumulación progresiva de material amiloide, hialino o mixto en las distintas capas corneales produce disminución de la transparencia corneal. Se describen las características clínicas y los estudios moleculares del gen TGFBI en una paciente Mexicana con una distrofia corneal estromal de tipo granular. Métodos: Examen oftalmológico completo, caracterización fenotípica de la distrofia corneal, y análi-sis del gen TGFBI por reacción en cadena de la polimerasa (PCR) y por secuenciación nucleotídica, en DNA de la propósita y de un hermano afectado. Resultados: Las lesiones corneales observadas en la paciente fueron compatibles con el diagnóstico de distrofia corneal estromal de tipo granular (clásica). No se observaron lesiones en las otras capas corneales. El análisis del gen TGFBI en DNA de la paciente y de un hermano afectado reveló una mutación puntual, de adenina a guanina, en el exón 14 de TGF-BI que origina un cambio de histidina a arginina en el aminoácido 626 (H626R) de la proteína TGFBI. Conclusiones: Éste es el primer caso en el que se demuestra que una distrofia corneal granular es ARTÍCULO ORIGINAL ABSTRACT Objective: To describe the clinical data and the results of molecular analyses of the TGFBI gene in a patient with classic granular stromal corneal dystrophy (type I). Methods: A female patient aged 60-years complaining of a long-standing decrease of visual acuity bilaterally associated with photophobia and foreign body sensation, underwent a complete ophthalmologic examination. Molecular analyses of DNA from the patient and from an affected brother included PCR amplification of exons 4, 11, 12, and 14 of the TGFBI gene and direct automated sequencing of the PCR products. Results:The affected patient showed a pattern of corneal stromal lesions that was compatible with a diagnosis of classic granular dystrophy. No involvement of other corneal layers was evident. Molecular analysis disclosed a point mutation in exon 14 of the TGFBI gene which consisted of an adenine to guanine change at nucleotide position 1924, predicting a substitution of arginine instead of histidine at residue 626 of the TGFBI protein (H626R). An identical mutation was detected in DNA from her affected brother.

Clinical and Histopathologic Characteristics and Template of the TGFBI p.(His626Arg) Missense Variant Lattice Corneal Dystrophy

“…Of over 2 dozen reported variant lattice dystrophies, the one caused by the missense variant c.1877A>G (previously denoted c.1924A>G) in exon 14 of TGFBI , which leads to p.(His626Arg) substitution (H626R in short form), appears to be the most frequently reported one to cause a variant LCD, 4,6–26 called either type I/IIIA or IIIB in the past. 8,13,14,22,23,26 This particular lattice corneal dystrophy variant, which we abbreviate LCDV-H626R, was first identified in France and Great Britain, but in addition to other European countries, it is often encountered in Asian and South American populations.…”