Cicatricial changes in ocular pemphigus.

PURPOSE: To describe the clinical characteristics of ocular involvement in patients with pemphigus at an ophthalmological referral center. METHODS: A retrospective review was conducted on patients with the immunopathological diagnosis of pemphigus examined between 1 January 2000 and 1 April 2010. Uncorrected distance visual acuity (UDVA), best corrected distance visual acuity (BCVA), ocular symptoms, and ocular surface inflammatory and scarring changes were assessed. RESULTS: A total of 15 patients were identified, with a mean age of 68.27 ± 14.35 years, and 80% (n=12) were female. Extraocular involvement was reported in one patient. All of the eyes showed cicatricial changes in the conjunctiva. In all, 6 eyes (20%) were classified as stage I; 12 eyes (40%) as stage II; 10 eyes (33%) as stage III; and 2 eyes (7%) as stage IV. A statistically significant association was found between BCVA and the severity of ocular involvement. The mean BCVA logMAR was 1.66 (20/914), with a range from logMAR 0 (20/20) to logMAR 4 (NLP). Other ocular diseases were found in 8 (53.3%), systemic diseases in 10 (66.7%), and the use of pemphigus-inducing drugs in 10 patients (66.7%). CONCLUSIONS: The present report represents the largest series of ocular involvement in pemphigus confirmed by immunopathology. The clinical manifestations varied from conjunctival hyperemia to corneal scarring and perforation. There was a strong association between scarring changes and low BCVA. Ocular and systemic diseases as well as the use of pemphigus-inducing drugs may predispose to ocular cicatricial changes observed in this series.

[PCR-based detection of heteroplasmic deleted mitochondrial DNA in Kearns-Sayre syndrome]. / Detección de deleciones en DNA mitocondrial heteroplásmico por medio de PCR EN el síndrome de Kearns-Sayre.

OBJECTIVE: To describe the clinical data and the results of molecular analyses of the mitochondrial DNA in a patient with Kearns-Sayre Syndrome. METHODS: Molecular analyses of mitochondrial DNA from the patient included PCR amplification of a region where the common Kearns- Sayre deletion is located and Genotype-Phenotype correlations are discussed. RESULTS: The affected patient showed ptosis, progressive external ophthalmoplegia, pigmentary changes in the peripheral retina and right bundle block. Molecular analysis disclosed a approximately 5 kb deletion in the mitochondrial DNA and some wild type mtDNA indicating heteroplasmy. CONCLUSIONS: Molecular analysis of mitochondrial DNA confirmed the clinical diagnosis of Kearns-Sayre syndrome. PCR provides a rapid method to identify the common 4997 bp deletion in Kearns-Sayre syndrome. In such cases, PCR diagnosis could avoid invasive methods such as muscle biopsy or spinal tap.

Detección de deleciones en DNA mitocondrial heteroplásmico por medio de PCR en el síndrome de Kearns-Sayre / PCR-based detection of heteroplasmic deleted mitochondrial DNA in Kearns-Sayre syndrome

Objetivo: El síndrome de Kearns-Sayre (SKS) esun trastorno neuromuscular causado por defectosgenéticos en el DNA mitocondrial siendo delecionesde tamaño variable la alteración mas común. Sedescriben las características clínicas y los resultadosdel análisis molecular del DNA mitocondrial enuna paciente Mexicana con Síndrome de Kearns-Sayre.Métodos: Examen oftalmológico completo, caracterizaciónfenotípica del Síndrome de Kearns-Sayrey análisis del DNA mitocondrial mediante reacciónen cadena de la polimerasa (PCR). Se discutencorrelaciones genotipo-fenotipo.Resultados: La paciente afectada mostró ptosis,oftalmoplejia progresiva externa cambios pigmentariosen retina periférica y bloqueo de rama derechadel haz de His. Los análisis moleculares revelaronuna deleción de ~5 kb en el DNA mitocondrial además de trazas de DNA sin alteraciones indicandoheteroplasmia.Conclusiones: El análisis molecular del DNAmitocondrial confirmó el diagnostico clínico de síndromede Kearns-Sayre. La utilización de PCR,como se describe en este trabajo, es un método rápidoy económico para el diagnóstico de la delecióncomún de 4977 pb en el síndrome de Kearns-Sayre.En estos casos, el diagnóstico por PCR evitaría procedimientosdiagnósticos invasivos y traumáticoscomo biopsia muscular o punción lumbar

Objective: To describe the clinical data and theresults of molecular analyses of the mitochondrialDNA in a patient with Kearns-Sayre Syndrome.Methods: Molecular analyses of mitochondrialDNA from the patient included PCR amplificationof a region where the common Kearns- Sayre deletionis located and Genotype-Phenotype correlationsare discussed.Results: The affected patient showed ptosis, progressiveexternal ophthalmoplegia, pigmentarychanges in the peripheral retina and right bundleblock. Molecular analysis disclosed a ~5kb deletionin the mitochondrial DNA and some wild type mtDNAindicating heteroplasmy.Conclusions: Molecular analysis of mitochondrialDNA confirmed the clinical diagnosis of Kearns-Sayre syndrome. PCR provides a rapid method toidentify the common 4997 bp deletion in Kearns Sayre syndrome. In such cases, PCR diagnosiscould avoid invasive methods such as musclebiopsy or spinal tap

[Autosomal dominant granular corneal dystrophy caused by a TGFBI gene mutation in a Mexican family]. / Distrofia corneal granular autosómica dominante causada por mutación del gen TGFBI en una familia Mexicana.

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. CONCLUSIONS: This is the first time that a case of stromal granular dystrophy has been demonstrated to be caused by the H626R mutation, a molecular defect classically detected in the phenotypically distinct lattice corneal dystrophy. Our data indicate that the same molecular defects in the TGFBI gene lead to different phenotypes in stromal dystrophies, thus expanding the genotypic-phenotypic spectrum in this group of corneal diseases.

Distrofia corneal granular autosómica dominante causada por mutación del gen TGFBI en una familia mexicana / Autosomal dominant granular corneal dystrophy caused by a TGFBI gene mutation in a mexican family

Objetivo: Las distrofias corneales son un grupo dealteraciones hereditarias en las que una acumulaciónprogresiva de material amiloide, hialino o mixtoen las distintas capas corneales produce disminuciónde la transparencia corneal. Se describen lascaracterísticas clínicas y los estudios molecularesdel gen TGFBI en una paciente Mexicana con unadistrofia corneal estromal de tipo granular.Métodos: Examen oftalmológico completo, caracterizaciónfenotípica de la distrofia corneal, y análisisdel gen TGFBI por reacción en cadena de lapolimerasa (PCR) y por secuenciación nucleotídica,en DNA de la propósita y de un hermano afectado.Resultados: Las lesiones corneales observadas en lapaciente fueron compatibles con el diagnóstico dedistrofia corneal estromal de tipo granular (clásica).No se observaron lesiones en las otras capas corneales.El análisis del gen TGFBI en DNA de la pacientey de un hermano afectado reveló una mutaciónpuntual, de adenina a guanina, en el exón 14 de TGFBIque origina un cambio de histidina a arginina enel aminoácido 626 (H626R) de la proteína TGFBI.Conclusiones: Éste es el primer caso en el que sedemuestra que una distrofia corneal granular es distrocausadapor la mutación H626R en TGFBI. Estamutación ha sido reportada consistentemente en ladistrofia estromal de tipo empalizada, clínicamentediferente a la granular. Nuestros datos indican queexisten excepciones en la aparente correlacióngenotipo-fenoitipo establecida en el grupo de distrofiascorneales asociadas a mutación en el genTGFBI

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. Conclusions: This is the first time that a case of ;;stromal granular dystrophy has been demonstrated ;;to be caused by the H626R mutation, a molecular ;;defect classically detected in the phenotypically ;;distinct lattice corneal dystrophy. Our data indicate ;;that the same molecular defects in the TGFBI gene ;;lead to different phenotypes in stromal dystrophies, ;;thus expanding the genotypic-phenotypic spectrum ;;in this group of corneal diseases