Identification of a Novel Missense KRT12 Mutation in a Vietnamese Family with Meesmann Corneal Dystrophy.

Meesmann epithelial corneal dystrophy (MECD) is a rare dominantly inherited disorder that is characterized by corneal epithelial microcysts and is associated with mutations in the keratin 3 (KRT3) and keratin 12 (KRT12) genes. In this study, we report a novel mutation in the KRT12 gene in a Vietnamese pedigree with MECD. Slit-lamp examination was performed on each of the 7 recruited members of a Vietnamese family to identify characteristic features of MECD. After informed consent was obtained from each individual, genomic DNA was isolated from saliva samples and screening of KRT3and KRT12 genes was performed by Sanger sequencing. The proband, a 31-year-old man, complained of a 1-year history of eye irritation and photophobia. Slit-lamp examination revealed intraepithelial microcysts involving only the corneal periphery in each eye with clear central corneas and no stromal or endothelial involvement. Three family members demonstrated similar intraepithelial microcysts, but with diffuse involvement, extended from limbus to limbus. Sanger sequencing of KRT3 (exon 7) and KRT12 (exons 1 and 6) in the proband revealed a novel heterozygous KRT12 variant (c.1273G>A [p.Glu425Lys]) that was present in the three affected family members but was absent in the three family members with clear corneas. This study is the first report of a Vietnamese family affected with MECD, associated with an atypical peripheral corneal epithelial phenotype in the proband and a novel mutation in KRT12.

Distrofia corneal de Meesmann en paciente con queratotomía hexagonal / Meesmann corneal dystrophy in a patient with hexagonal keratotomy

RESUMEN Las distrofias corneales constituyen un grupo de enfermedades hereditarias que suelen ser bilaterales y simétricas, las cuales progresan lentamente y sin relación con factores ambientales o sistémicos. Se presenta una paciente de raza blanca, de 45 años de edad, remitida al Servicio de Córnea del Instituto Cubano de Oftalmología "Ramón Pando Ferrer", quien refirió sensación de cuerpo extraño, sensibilidad a la luz y mala visión de ambos ojos, así como antecedente de queratotomía hexagonal hacía aproximadamente 20 años. En lámpara de hendidura se observaron en el epitelio numerosas lesiones puntiformes en forma de vesículas claras, semejantes a ampollas, distribuidas paracentralmente, que respetaban ligeramente el centro, con espacios de córnea transparente entre ellas y mejor visibilidad de las lesiones en retroiluminación. En la microscopia confocal se observaron en el ojo derecho estructuras redondas u ovales, de forma quística, hiporreflectivas. En el ojo izquierdo se encontraron imágenes difusas hiperreflectivas en el epitelio corneal basal. Se detectó la presencia de nervios corneales tortuosos, de aspecto fragmentado en ambos ojos. Se consideró como diagnóstico la distrofia de Meesmann y se realizó queratectomía superficial, con lo cual se logró alivio de la sintomatología de la paciente(AU)

ABSTRACT Corneal dystrophies are a group of hereditary diseases often bilateral and symmetrical which progress slowly and without any relationship to environmental or systemic factors. A case is presented of a white 45-year-old female patient referred to the Cornea Service of Ramón Pando Ferrer Cuban Institute of Ophthalmology, who reported a foreign body sensation, light sensitivity and poor vision in both eyes, as well as a history of hexagonal keratotomy from approximately 20 years before. Slit lamp examination revealed numerous punctiform lesions in the form of clear blister-like vesicles distributed paracentrally and slightly sparing the center, with transparent cornea spaces between them and better visibility of the lesions under retroillumination. Confocal microscopy showed round or oval cystic and hyporeflective structures in the right eye, whereas the left eye exhibited diffuse hyperreflective images in the basal corneal epithelium. Tortuous corneal nerves of a fragmented appearance were detected in both eyes. A Meesmann dystrophy diagnosis was considered and superficial keratectomy was performed, with which the patient's symptoms were relieved(AU)

In vivo histology and p.L132V mutation in KRT12 gene in Japanese patients with Meesmann corneal dystrophy.

PURPOSE: To report genetic mutational analysis and in vivo histology of Meesmann corneal dystrophy. STUDY DESIGN: Prospective, case control study. METHODS: Six patients from three independent families with clinically diagnosed Meesmann corneal dystrophy were enrolled in this study. Slit-lamp biomicroscopy with fluorescein vital staining, anterior segment optical coherence tomography (AS-OCT), and in vivo laser confocal microscopy (IVCM) were performed on selected patients. Mutational screening for the keratin genes KRT3 and KRT12 was performed in all six patients and selected unaffected family members. RESULTS: Slit-lamp biomicroscopy revealed numerous intraepithelial microcysts in all affected individuals. AS-OCT revealed hyperreflectivity and high corneal epithelial layer thickness (mean, 64.8µm) in all individuals tested (3/3). By using IVCM, multiple epithelial microcysts and hyperreflective materials (6/6), subepithelial nerve abnormalities (6/6), tiny punctate hyperreflective material (6/6), and needle-like hyperreflective materials (4/6) were observed in the corneal stromal layer. A heterozygous genetic mutation in the KRT12 gene (c.394 C>G, p.L132V) was identified in all six patients. No pathological mutation was observed in the KRT3 gene. CONCLUSION: We identified a heterozygous genetic mutation (c.394 C>G, p.L132V) in the KRT12 gene in six Japanese patients with inherited Meesmann corneal dystrophy. This is the first study to confirm this genetic mutation in Japanese Meesmann corneal dystrophy patients. This mutation has been independently reported in an American Meesmann corneal dystrophy patient, confirming its pathogenicity. AS-OCT and IVCM proved to be useful tools for observing corneal epithelial layer pathology in this dystrophy. Furthermore, IVCM reveals corneal stromal layer pathological changes not previously reported in this dystrophy.