RESUMEN
The purpose of this study was to investigate the early alterations of retinal function, assessed with electrophysiology, in newly onset type 2 diabetes patients without vascular retinopathy. Seventeen patients with newly diagnosed type 2 diabetes (duration 7±3 months), without any vascular retinopathy in fundus photographs, were examined with full-field electroretinogram (ERG) and multifocal ERG (mfERG). The results were compared with those of age-matched subjects without diabetes. In the dark-adapted full-field ERG, the a-wave and the 30-Hz flicker implicit times were delayed in diabetes patients compared to controls, P=0.001 and P=0.020. In the first-order kernel of the mfERG, the first positive wave, P1, was delayed in all areas measured. The electrophysiological examinations demonstrate early alterations of retinal function characterised by a delayed a-wave implicit time in the dark-adapted full-field ERG, representing the rod signalling, and alterations in the multifocal ERG reflecting cone and/or postreceptoral function.
Asunto(s)
Adaptación a la Oscuridad/fisiología , Diabetes Mellitus Tipo 2/fisiopatología , Electrorretinografía/métodos , Retina/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Enfermedades de la Retina/fisiopatología , Índice de Severidad de la EnfermedadRESUMEN
PURPOSE: To evaluate retinal function and histopathology in rabbits treated orally with the anti-epileptic drug topiramate. METHODS: Six rabbits were treated with a daily oral dose of topiramate during a period of eight months. Six rabbits receiving water served as controls. Blood samples were analyzed for determination of topiramate serum levels in order to ensure successful drug exposition. Standardized full-field electroretinograms (ERGs) were performed before treatment and then at 2, 3 and 8 months during the treatment period. After terminating treatment the rabbits were sacrificed and the morphology of the sectioned retina was studied. RESULTS: After eight months of treatment the full-field ERG demonstrated normal rod function in treated and control rabbits, but the light adapted 30 Hz flicker b-wave amplitude was significantly reduced in the treated rabbits. This was the case for both the light adapted (Wilcoxon signed ranks test, P = 0.046) and the dark adapted (Wilcoxon signed ranks test, P = 0.028) 30 Hz flicker response from the treated rabbits. Retinal immunohistology revealed a severe accumulation of GABA in amacrine cells and in the inner plexiform layer in 4 of 6 treated rabbits compared to the controls. CONCLUSIONS: Topiramate, orally administrated to rabbits, may cause a significant reduction of the retinal function demonstrated by the reduced b-wave amplitude in the full-field ERG, as well as changes in immunohistology characterized by a severe accumulation of GABA in the inner retina. The retinal dysfunction and the morphological changes indicate that topiramat may damage the retina, similarly to vigabatrin (another anti-epileptic drug).
Asunto(s)
Anticonvulsivantes/farmacología , Electrorretinografía , Fructosa/análogos & derivados , Retina/efectos de los fármacos , Retina/patología , Adaptación Ocular , Administración Oral , Células Amacrinas/metabolismo , Animales , Anticonvulsivantes/administración & dosificación , Adaptación a la Oscuridad , Esquema de Medicación , Fructosa/administración & dosificación , Fructosa/farmacología , Inmunohistoquímica , Estimulación Luminosa/métodos , Conejos , Retina/metabolismo , Retina/fisiopatología , Distribución Tisular , Topiramato , Ácido gamma-Aminobutírico/metabolismoRESUMEN
PURPOSE: To describe the clinical and electrophysiological findings in a young boy with decreased vision possibly due to retinal damage by rifabutin. METHODS: An 8-year-old boy with osteomyelitis was referred due to visual disturbance. During a period of 4 years, the boy was examined six times with electroretinography. Ophthalmological examination included testing of visual acuity, slit-lamp inspection, fundus inspection, fundus photography and kinetic perimetry. Two electrophysiological methods were performed for objective evaluation of retinal function, namely full-field electroretinography and multifocal electroretinography. RESULTS: We found a slightly reduced visual acuity, a slowly increasing amount of yellow-white deposits on the posterior surface of the cornea and on the anterior part of the lens, a normal fundus appearance, and normal visual fields. However, the electroretinogram was abnormal on several occasions during therapy with rifabutin, but returned to normal 3 months after withdrawal of the medication. The multifocal electroretinogram returned to normal after the full-field electroretinogram had done so. The anterior chamber deposits still remain. CONCLUSION: Long-term treatment with rifabutin may have a reversible and previously undescribed side-effect on retinal function. The drug may also accumulate irreversibly on the posterior surface of the cornea and on the anterior surface of the lens. We suggest that objective evaluation of retinal function with electrophysiological methods should be performed in patients with visual disturbance during treatment with rifabutin.
Asunto(s)
Segmento Anterior del Ojo/efectos de los fármacos , Antibióticos Antituberculosos/efectos adversos , Retina/efectos de los fármacos , Enfermedades de la Retina/inducido químicamente , Rifabutina/efectos adversos , Segmento Anterior del Ojo/patología , Niño , Electrorretinografía , Humanos , Masculino , Osteomielitis/complicaciones , Osteomielitis/tratamiento farmacológico , Retina/fisiología , Enfermedades de la Retina/fisiopatología , Agudeza Visual , Campos VisualesRESUMEN
PURPOSE: To characterize the clinical phenotype, with emphasis on electrophysiology, of two children with suspected Bothnia dystrophy. METHODS: Two unrelated affected patients, 10 and 11 years old, were studied. Ophthalmological examination included testing of visual acuity, fundus inspection and fundus photography, kinetic perimetry, full-field electroretinogram (ERG), and multifocal ERG. The presence of a mutation in exon 7 of the RLBP1 gene was investigated by DNA sequencing. RESULTS: Both patients were homozygous for the Arg234Trp-causing mutation in the RLBP1 gene, but the resulting disease phenotype appeared to vary somewhat between them. Visual acuity was moderately reduced in one patient and normal in the other. Fundus inspection at this age revealed no pathology in either patient and there were no signs of retinitis punctata albescens, which has been described previously as a frequent clinical feature of Bothnia dystrophy. The result of kinetic perimetry was normal. The final rod threshold was moderately elevated. Full-field ERG demonstrated the uncommon combination of absent rod response and normal cone response after 40 minutes of dark adaptation. However, after prolonged dark adaptation (20-24 h), both the rod response and the dark adaptation threshold became normal. Multifocal ERG was performed in one of the patients (the one with normal visual acuity and normal fundus appearance) and showed a reduced cone response in the central region of the tested area. There was no improvement of the multifocal ERG result after 20-24 h of dark adaptation. CONCLUSION: Patients with mutations in the RLBP1 gene (Arg234Trp) may have a normal fundus appearance early in the disease course. Multifocal ERG can be used for the objective documentation of the disturbed macular function, especially when the patient's visual acuity and fundus appearance are normal. The rod response is absent in the electroretinogram; however, after prolonged dark adaptation (20-24 hours), the rods recover completely. The central cones do not seem to recover.
Asunto(s)
Proteínas Portadoras/genética , Mutación , Células Fotorreceptoras de Vertebrados/fisiología , Degeneración Retiniana/fisiopatología , Niño , Adaptación a la Oscuridad , Diagnóstico Diferencial , Electrorretinografía , Femenino , Angiografía con Fluoresceína , Fondo de Ojo , Humanos , Procesamiento de Imagen Asistido por Computador , Fenotipo , Reacción en Cadena de la Polimerasa , Degeneración Retiniana/etnología , Degeneración Retiniana/genética , Umbral Sensorial , Suecia/epidemiología , Agudeza Visual , Campos VisualesRESUMEN
PURPOSE: To examine the retinal function with different electrophysiological methods in twelve Swedish patients on long-term treatment (2-10 years) with the anti-epileptic drug vigabatrin. METHODS: Ophthalmological examination of twelve consecutive patients included testing of visual acuity, fundus inspection and fundus photography, kinetic perimetry, full-field ERG and multifocal ERG. RESULTS: All patients had a visual acuity of 0.7 or better. Fundus inspection revealed no pathology except in one patient who had a pallor of the optic disc. All patients had a normal appearance of the macula. The result of kinetic perimetry was normal in five patients while seven patients had a concentric defect of the visual field. The 30 Hz flicker cone b-wave amplitude in the full-field ERG was abnormal in all of the seven patients with a visual field defect. None of the patients with normal visual fields had a reduction of the 30 Hz flicker cone b-wave amplitude. Six of the twelve patients had a reduced multifocal ERG response but without any correlation with visual field defect. CONCLUSION: Long-term treatment with vigabatrin seems to selectively reduce retinal cone function. The visual field defects in patients taking vigabatrin correlate with pathology in the full-field ERG (reduction of the cone b-wave amplitude). The results from this study indicate that electroretinography can be used for monitoring patients taking vigabatrin in a more objective manner than with visual field testing.
Asunto(s)
Anticonvulsivantes/efectos adversos , Electrorretinografía/métodos , Células Fotorreceptoras Retinianas Conos/efectos de los fármacos , Enfermedades de la Retina/inducido químicamente , Enfermedades de la Retina/fisiopatología , Vigabatrin/efectos adversos , Campos Visuales/efectos de los fármacos , Adulto , Anciano , Anticonvulsivantes/uso terapéutico , Humanos , Persona de Mediana Edad , Células Fotorreceptoras Retinianas Conos/fisiopatología , Vigabatrin/uso terapéutico , Trastornos de la Visión/inducido químicamente , Trastornos de la Visión/fisiopatología , Agudeza Visual/efectos de los fármacos , Pruebas del Campo VisualRESUMEN
PURPOSE: To investigate, using full-field ERG, the retinal function in patients with Batten/Spielmeyer-Vogt disease caused by mutations in the CLN(3) gene. METHODS: Batten disease status of five patients was confirmed by the presence of vacuolated lymphocytes in peripheral blood and the identification of mutations in the Batten disease gene (CLN(3)). Visual acuity, fundus appearance, and full-field ERG were examined in all patients (age 4-19 years). The examination was repeated in one patient after 16 months. RESULTS: Three unrelated patients were homozygous for the most common mutation in CLN(3), the 1.02 kb deletion; two patients (sisters) were heterozygous for the 1.02 kb deletion and an as yet unidentified mutation in the CLN(3) gene. Full-field ERG recordings in all five patients demonstrated no rod responses and only small remaining cone responses, which could be detected with 30 Hz-flicker stimulation. Re-examination of a six-year-old girl after 16 months revealed a fast progression of the retinal degeneration. CONCLUSION: Full-field ERG recordings in Batten disease patients, both homozygous and heterozygous for the 1.02 kb deletion in the CLN( 3) gene, confirm retinal degeneration to be severe, widespread, and with a rapid progression early in the disease course. The onset of visual failure may be delayed when compared to the classic disease course, particularly in patients who are not homozygous for the most common CLN(3) mutation, a 1.02 kb deletion. In that case, the disease progression in terms of other symptoms may also be further delayed.
Asunto(s)
Glicoproteínas de Membrana , Chaperonas Moleculares , Mutación , Lipofuscinosis Ceroideas Neuronales/genética , Lipofuscinosis Ceroideas Neuronales/fisiopatología , Proteínas/genética , Retina/fisiopatología , Degeneración Retiniana/fisiopatología , Adolescente , Adulto , Niño , Preescolar , ADN/análisis , ADN/sangre , Análisis Mutacional de ADN , Progresión de la Enfermedad , Electrorretinografía , Femenino , Angiografía con Fluoresceína , Humanos , Masculino , Reacción en Cadena de la Polimerasa , Degeneración Retiniana/genética , Agudeza VisualRESUMEN
OBJECTIVE: To describe the clinical phenotype of juvenile X-linked retinoschisis in patients with different mutations in the XLRS1 gene. METHODS: Thirty patients with 7 different XLRS1 mutations were examined. The genotype was determined by molecular genetics, which identified 6 known and 1 novel mutation (exon 5, 489 G-->T). Ophthalmologic examination included full-field electroretinogram (ERG) recordings. RESULTS: The fundus appearance showed marked variations between, as well as within, families with different XLRS1 mutations. The ERG demonstrated typical reduction of B-wave amplitude, with relative A-wave preservation, causing a reduced B-A ratio in all affected males. The implicit time of the 30-Hz flicker ERG was prolonged in all patients examined. In a large family with a deletion of exon 1 and the promoter region, 12 affected males showed a phenotype ranging from moderate to severe vision impairment and a broad range of ERG abnormality, suggesting that additional factors may contribute to the disease severity. CONCLUSIONS: Juvenile retinoschisis shows a wide variability in the phenotype between, as well as within, families with different genotypes. The ERG findings show reduced B-A ratios of dark-adapted recordings and prolonged implicit times of 30-Hz flicker response, which provide a useful clinical marker to confirm the clinical diagnosis. CLINICAL RELEVANCE: This study describes the wide variability in the phenotype in patients with juvenile retinoschisis and different mutations in the XLRS1 gene. The study emphasizes the importance of complementing the ophthalmologic examination with full-field ERG and molecular genetics in boys with visual failure of unknown etiology to determine the diagnosis early in the course of the disease. Arch Ophthalmol. 2000;118:1098-1104
Asunto(s)
Proteínas del Ojo/genética , Ligamiento Genético , Mutación , Degeneración Retiniana/genética , Cromosoma X , Adolescente , Adulto , Anciano , Niño , Preescolar , Electrorretinografía , Femenino , Fondo de Ojo , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Linaje , Fenotipo , Retina/fisiopatología , Degeneración Retiniana/fisiopatología , SueciaRESUMEN
We present the clinical and molecular genetic features of a large multi-generation Norwegian family with dominant cone-rod dystrophy. Ophthalmological evaluation including electroretinography showed cone dysfunction in younger patients, with rod dysfunction becoming apparent at more advanced stages of the disease. In one branch of the family, cone degeneration remained the only manifestation despite advancing age. Linkage analysis mapped the disease gene in this family to 17p12-p13, a chromosome region previously linked to cone-rod dystrophy in a Swedish family (CORD5). A maximum LOD score of 3.25 (straight theta = 0.00) for marker D17S1844 was obtained. Mutation analysis of the guanylate cyclase 2D gene (GUCY2D, MIM 600179, previously called RETGC1), located at 17p12-p13, showed a missense mutation (R838C) in exon 13, that co-segregated with the eye disease in the family. Our suspicion of the possibility of an interrelationship between the Swedish CORD5 family and the present family, both originating from Northern Scandinavia, initiated the linkage analysis in the Norwegian family. The R838C missense mutation was not, however, detected in the Swedish patients, strongly suggesting no relationship between these two families. The long-term ophthalmological evaluation in this large four-generation family, combined with the identification of the disease-causing mutation, provide critical information for refining the classification, prognosis, and genetic counselling of patients with cone-rod dystrophies.
Asunto(s)
Guanilato Ciclasa/genética , Mutación Missense , Células Fotorreceptoras de Vertebrados/patología , Degeneración Retiniana/genética , Adulto , Anciano , Niño , Cromosomas Humanos Par 17/genética , Defectos de la Visión Cromática/genética , Defectos de la Visión Cromática/fisiopatología , Análisis Mutacional de ADN , Electrorretinografía , Femenino , Genes Dominantes , Ligamiento Genético , Humanos , Escala de Lod , Masculino , Persona de Mediana Edad , Linaje , Células Fotorreceptoras de Vertebrados/enzimología , Reacción en Cadena de la Polimerasa , Degeneración Retiniana/enzimología , Degeneración Retiniana/fisiopatología , Células Fotorreceptoras Retinianas Bastones/enzimología , Células Fotorreceptoras Retinianas Bastones/fisiología , Agudeza Visual , Campos VisualesRESUMEN
OBJECTIVE: To examine the clinical phenotype of three Swedish families with Best's vitelliform macular dystrophy (BMD) and three different mutations in the recently identified bestrophin gene. METHODS: Three families, including 13 patients, were examined clinically using visual acuity testing, electro-oculography, fundus inspection, and fundus photography. The mutations were previously determined by direct sequence analysis of the individual exons in the bestrophin gene. RESULTS: The largest family (SL76), with the Y85K (T357C) mutation in the bestrophin gene, demonstrated a clinical phenotype characterized by a variable degree of visual acuity reduction and a marked intrafamilial variability in macular pathology. The electro-oculograms, however, demonstrated similar results in all patients regardless of the severity of the macular dysfunction. The smallest family (SL3), with the mutation V9A (T130C) in the bestrophin gene, and the family (SL2) with the mutation D104E (C416A) demonstrated a similar clinical phenotype. The majority of patients (11/13 examined subjects) had a binocular visual acuity of 20/63 or better at a late stage of the disease course, indicating a relatively good prognosis for visual acuity in this specific phenotype. The ophthalmoscopic changes were followed in one of the patients for 38 years and in three of the patients for 19 years and showed that the macular appearance seems to be stable after adolescence. CONCLUSIONS: Patients with BMD and mutations in the bestrophin gene have a similar clinical phenotype characterized by a variable, but relatively moderate visual acuity reduction, atrophic changes in the macula, and pathological results of the electro-oculograms. The macular appearance remains essentially unchanged through the atrophic stage (stage IV) in the majority of patients, indicating a stationary disease course associated with this specific genotype.
Asunto(s)
Proteínas del Ojo/genética , Degeneración Macular/patología , Adolescente , Adulto , Anciano , Sustitución de Aminoácidos , Bestrofinas , Niño , Preescolar , Canales de Cloruro , ADN/química , ADN/genética , Análisis Mutacional de ADN , Electrooculografía , Electrorretinografía , Salud de la Familia , Femenino , Fondo de Ojo , Humanos , Degeneración Macular/genética , Masculino , Persona de Mediana Edad , Mutación , Linaje , Suecia , Agudeza VisualRESUMEN
PURPOSE: To clinically characterize a Swedish family with autosomal dominant retinitis pigmentosa due to a mutation, Arg-172-Trp, in the peripherin/RDS gene. METHODS: Full clinical evaluation including kinetic visual field testing, measurement of dark-adaptation threshold, and full-field electroretinography in seven patients with autosomal dominant retinitis pigmentosa and three healthy family members. Denaturing gradient gel electrophoresis (DGGE) was used for mutation screening in seven patients and six healthy members of the family. RESULTS: Three of four siblings from the middle generation and four of the younger generation were heterozygous for the peripherin /RDS Arg-172-Trp mutation. The mutation segregated with the disease. Visual acuity decreased progressively with age and visual fields were moderately constricted in young patients, while central scotoma and constriction of the fields were detected in the family members above 50 years of age. The results from full-field electrography were comparable with a widespread retinal degeneration. CONCLUSIONS: Earlier, the peripherin/RDS Arg-172-Trp mutation was associated primarily with a macular degeneration phenotype. One previous study indicated that this mutation also can give rise to a degeneration of the more peripheral parts of the retina. In the present study, a widespread retinal degeneration is seen in the patients above 50 years of age, carrying the Arg-172-Trp mutation.
Asunto(s)
Proteínas de Filamentos Intermediarios/genética , Glicoproteínas de Membrana , Mutación/genética , Proteínas del Tejido Nervioso/genética , Degeneración Retiniana/genética , Adulto , Sustitución de Aminoácidos , Progresión de la Enfermedad , Electrorretinografía , Femenino , Fondo de Ojo , Humanos , Masculino , Persona de Mediana Edad , Linaje , Periferinas , Degeneración Retiniana/patología , Degeneración Retiniana/fisiopatología , Retinitis Pigmentosa/genética , Suecia , Pruebas del Campo VisualRESUMEN
PURPOSE: To characterize the clinical phenotype, with emphasis on electrophysiology, of members of a Swedish family with autosomal dominant retinitis pigmentosa due to a novel mutation, F211L, in the peripherin/RDS gene. METHODS: Nine patients with autosomal dominant retinitis pigmentosa and two healthy family members underwent a full clinical evaluation including kinetic visual field testing, measurement of dark adaptation threshold, and full-field electroretinography. Blood samples were collected and DNA analysis was performed using denaturing gradient gel electrophoresis (DGGE). RESULTS: The grandfather, six of seven siblings from the middle generation, and two young boys carried the mutation F211L in the peripherin/RDS gene. The mutation segregated with the clinical presentation of disease. Fundus examination revealed mainly macular atrophy. All assessed parameters of retinal function (visual acuity, dark adaptation threshold, visual fields, and full-field electroretinograms) demonstrated a successive reduction with increasing age. Full-field electroretinograms showed a diminished rod response in all affected individuals and a reduction of the cone b-wave amplitudes with increasing age, indicating retinitis pigmentosa. In the affected family members, the disease seems to progress at a similar rate with increasing age. CONCLUSIONS: The peripherin/RDS gene mutation F211L is associated with a clinical phenotype and includes early loss of rod function and successive reduction of cone function with increasing age, but impressively well-preserved visual acuity and visual fields in young and middle-aged patients and moderately reduced vision in the old patient. Compared to previously described phenotypes segregating with mutations in the peripherin/RDS gene, the present family demonstrates a more benign clinical phenotype, which is concordant within the family.
Asunto(s)
Genes Dominantes , Variación Genética/genética , Proteínas de Filamentos Intermediarios/genética , Glicoproteínas de Membrana , Proteínas del Tejido Nervioso/genética , Retinitis Pigmentosa/genética , Adolescente , Adulto , Anciano , Secuencia de Aminoácidos , Niño , Adaptación a la Oscuridad/fisiología , Electrorretinografía , Fondo de Ojo , Humanos , Datos de Secuencia Molecular , Mutación/genética , Linaje , Periferinas , Fenotipo , Refracción Ocular/fisiología , Retinitis Pigmentosa/patología , Retinitis Pigmentosa/fisiopatología , Umbral Sensorial/fisiología , Agudeza Visual/fisiología , Campos Visuales/fisiologíaRESUMEN
PURPOSE: To examine the clinical phenotype with emphasis on electroretinograms and visual fields in a Swedish family with X-linked retinitis pigmentosa (XLRP) type 2 (RP2), and compare it with Swedish XLRP families with the RP3 genotype. METHODS: Three affected brothers and their carrier mother were examined clinically and with kinetic perimetry, dark adaptation thresholds, and full-field electroretinograms. The genotype was determined by haplotype analysis using polymorphic markers spanning the XLRP loci at the short arm of the X chromosome. RESULTS: The phenotype was consistent in the three affected males. The first subjective symptom was night blindness and the visual disability was more pronounced with increasing age. Affected individuals had a slight decrease in visual acuity and were emmetropic. They demonstrated a pathologically elevated final rod threshold. The visual fields were constricted in a somewhat atypical pattern. The three patients had an early presenting atypical cataract with multiple opacities. The fundus appearance was typical for RP with narrowing of retinal vessels and bone spicule pigmentations. The rod electroretinograms were extinguished in both eyes of the patients. The combined rod-cone responses as well as the isolated cone responses were severely reduced in amplitude; however, atypically for RP, the implicit time for the isolated cone responses was normal. The carrier female demonstrated normal ophthalmological findings, with the exception of two minimal pigmentations in the lower quadrants of the left eye. Haplotype analysis demonstrated that the disease in this family segregates with the RP2 locus. CONCLUSION: The phenotype of the studied RP2 family is associated with early onset of night blindness, emmetropia, a slight decrease in visual acuity, constriction of visual fields, and atypical cataract formation. Electroretinograms demonstrate severe rod dysfunction and surprisingly normal cone response implicit times which may indicate a milder disease progression. These findings are different from earlier descriptions of the RP2 and RP3 phenotypes.
Asunto(s)
Ligamiento Genético , Retinitis Pigmentosa/genética , Cromosoma X , Adolescente , Adulto , Catarata/complicaciones , Adaptación a la Oscuridad/fisiología , Electrorretinografía , Femenino , Ligamiento Genético/genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Linaje , Refracción Ocular/fisiología , Retinitis Pigmentosa/complicaciones , Retinitis Pigmentosa/fisiopatología , Umbral Sensorial/fisiología , Suecia , Agudeza Visual/fisiología , Campos Visuales/fisiología , Cromosoma X/genéticaRESUMEN
AIMS: To develop a sensitive mutation screening procedure suitable for routine analysis of the peripherin/RDS gene, and to estimate the nature and prevalence of peripherin/RDS gene mutations in Swedish patients with autosomal dominant retinitis pigmentosa. METHODS: To make the method as sensitive as possible, as many as eight segments, covering the three exons and the flanking intron sequences of the peripherin/RDS gene, were analysed by denaturing gradient gel electrophoresis. A group of 38 Swedish patients with a clinical diagnosis of autosomal dominant retinitis pigmentosa were screened for mutations in the peripherin/RDS gene. RESULTS: Three point mutations were found in four of the patients and five polymorphisms were defined. One mutation in exon 1, R172W, has been described previously in other ethnic groups as causing a macular degeneration. Another mutation, in exon 2 and causing the substitution F211L, was found in two unrelated patients. A third mutation, resulting in the likely non-pathogenic substitution S289L, as well as a polymorphism not reported previously, was found in exon 3. CONCLUSIONS: The screening procedure described allows detection of mutations in all of the exons, including the polymorphic 5' and 3' ends of the gene, and is therefore suitable for routine screening of peripherin/RDS gene defects in patients with autosomal dominant retinitis pigmentosa. The frequency of mutations found in the Swedish patient group indicates that defects in the peripherin/RDS gene might be a more common cause of autosomal dominant retinitis pigmentosa than was thought previously.
Asunto(s)
Proteínas de Filamentos Intermediarios/genética , Glicoproteínas de Membrana/genética , Proteínas del Tejido Nervioso/genética , Mutación Puntual , Retinitis Pigmentosa/genética , Electroforesis/métodos , Exones , Femenino , Genes Dominantes , Humanos , Masculino , Linaje , Periferinas , Reacción en Cadena de la PolimerasaRESUMEN
PURPOSE: To assess the clinical phenotypes in three Swedish families with X-linked retinitis pigmentosa caused by different mutations in the RPGR gene. METHODS: Three families from different parts of Sweden, including nine patients with retinitis pigmentosa and six female carriers of X-linked retinitis pigmentosa, were examined clinically. Ophthalmologic examination included kinetic perimetry with a Goldmann perimeter using standardized objects I4e and V4e, dark adaptation final thresholds with a Goldmann-Weeker adaptometer, and full-field electroretinograms. RESULTS: The clinical findings in the patients demonstrated a severe form of retinitis pigmentosa with visual handicap early in life. Patients with a microdeletion of exons 8 through 10 of the RPGR gene had a more severe phenotype compared to the patients with single base-pair mutations in the introns 10 and 13 of the RPGR gene, resulting in splicing defects. Furthermore, heterozygous carriers in these families displayed a wide spectrum of clinical features, from minor symptoms to severe visual disability. CONCLUSION: These three families show a variable clinical phenotype resulting from different mutations in the RPGR gene. A microdeletion spanning at least parts of exons 8 through 10 seems to result in a severe phenotype compared to the splice defects. Heterozygous carriers of X-linked retinitis pigmentosa with these specific RPGR genotypes also show a variability of the phenotype; carriers with the microdeletion may be severely visually handicapped.
Asunto(s)
Proteínas Portadoras/genética , Proteínas del Ojo , Ligamiento Genético , Mutación , Retinitis Pigmentosa/genética , Cromosoma X/genética , Adolescente , Adulto , Anciano , Niño , Deleción Cromosómica , Electrorretinografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Linaje , Fenotipo , Retinitis Pigmentosa/fisiopatología , Retinitis Pigmentosa/rehabilitación , Suecia , Agudeza Visual , Campos VisualesRESUMEN
By screening blood samples from patients with autosomal dominant retinitis pigmentosa, we found in one of the families a rhodopsin mutation (Pro-267-Leu), which segregates with the disease in two affected and five unaffected family members. Here, we present the results of the clinical evaluation of the family, including full-field electroretinography from the two affected family members. A 25-year-old family member with the mutation had an almost normal electrophysiological retinal response. The patient's father, who was also heterozygous for the mutation and had mild subjective symptoms of retinitis pigmentosa, demonstrated a substantially preserved retinal function. Our results suggest that the Pro-267-Leu rhodopsin mutation is associated with a very mild phenotype of retinitis pigmentosa. Young patients with the disease may have minimal pathological changes in the electroretinogram and some patients with few symptoms may be affected without acquiring a diagnosis of eye disease.
Asunto(s)
Aberraciones Cromosómicas , Trastornos de los Cromosomas , Genes Dominantes/genética , Mutación Puntual/fisiología , Prolina/genética , Retinitis Pigmentosa/genética , Retinitis Pigmentosa/fisiopatología , Rodopsina/genética , Adulto , Electrorretinografía , Exones/genética , Enfermedades Hereditarias del Ojo/genética , Enfermedades Hereditarias del Ojo/fisiopatología , Salud de la Familia , Femenino , Pruebas Genéticas , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , Linaje , Fenotipo , Mutación Puntual/genética , Análisis de Secuencia de ADN , Suecia , Agudeza Visual/genética , Agudeza Visual/fisiologíaRESUMEN
We here present the clinical phenotype in 6 patients from a family with autosomal dominant retinitis pigmentosa found to carry a point mutation in the rhodopsin gene (arginine-135-tryptophan). The mutation is the second found by mutation screening of DNA from 20 Swedish families with dominant retinitis pigmentosa. With full-field electroretinography we could document a severe form of retinitis pigmentosa in patients belonging to the family, similar to the phenotype associated with the previously reported mutation (arginine-135-leucine). Our results indicate that different point mutations in the same region of the rhodopsin gene, resulting in amino acids with similar properties (both hydrophobic), may cause a similar clinical phenotype. Further, point mutations in this specific region seem to cause an agressive form of retinitis pigmentosa.
Asunto(s)
Arginina/genética , Leucina/genética , Mutación Puntual/genética , Retinitis Pigmentosa/genética , Rodopsina/genética , Adolescente , Adulto , Niño , Análisis Mutacional de ADN , Cartilla de ADN/química , Electrorretinografía , Femenino , Fondo de Ojo , Genes Dominantes/genética , Pruebas Genéticas , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Linaje , Fenotipo , Reacción en Cadena de la Polimerasa , Retinitis Pigmentosa/patología , Retinitis Pigmentosa/fisiopatología , Campos VisualesRESUMEN
A family with a newly detected X-linked syndrome including sensorineural deafness, mental retardation, dystonia and blindness was examined with full-field electroretinography in order to order to find out if the blindness was caused by a retinal degeneration. Six affected males and 2 obligate carriers showed no signs of retinal degeneration. One of 7 affected males had central areolar choroidal dystrophy confirmed by central scotomas in visual fields and an electroretinographic pattern consisting of an attenuated amplitude as well as a prolonged implicit time of the cone b-wave on stimulation with 30 Hz flickering white light.
Asunto(s)
Ceguera/fisiopatología , Electrorretinografía , Síndromes Orofaciodigitales/complicaciones , Retina/fisiología , Adulto , Ceguera/complicaciones , Ceguera/patología , Enfermedades de la Coroides/complicaciones , Enfermedades de la Coroides/patología , Enfermedades de la Coroides/fisiopatología , Femenino , Fondo de Ojo , Humanos , Masculino , Persona de Mediana Edad , Síndromes Orofaciodigitales/genética , Síndromes Orofaciodigitales/fisiopatología , Linaje , Degeneración Retiniana/complicaciones , Degeneración Retiniana/patología , Degeneración Retiniana/fisiopatología , Escotoma/complicaciones , Escotoma/patología , Escotoma/fisiopatología , Agudeza VisualRESUMEN
Full-field electroretinograms were recorded from four infants (under the age of 12 months), with different types of tapetoretinal degeneration. Some of these patients, appear to have normal fundi. This article stresses the clinical usefulness of evaluation with electroretinography in young children.
Asunto(s)
Electrorretinografía , Células Fotorreceptoras/fisiopatología , Retinitis Pigmentosa/fisiopatología , Humanos , Lactante , Oftalmoscopía , Linaje , Retinitis Pigmentosa/congénitoRESUMEN
A Swedish family with choroideremia and a deletion of the CHM gene has been studied with ophthalmological examination, full-field electroretinography, and DNA analysis in order to characterize the phenotype of the disease. Although all four patients studied had a complete deletion of the gene, they showed a considerable variability regarding the phenotype, including the electroretinogram tracings. Two of the affected males demonstrated a severe form of choroideremia with low or nondetectable ERG recordings, while the other two affected males showed a less severe phenotype with only a slight reduction of the ERG amplitudes. The variation of the clinical phenotype among family members carrying the same mutation indicates that the severity of choroideremia is not solely a function of the CHM gene.
Asunto(s)
Coroideremia/genética , Genes , Variación Genética/genética , Adulto , Anciano , Niño , Coroideremia/patología , Coroideremia/fisiopatología , Análisis Mutacional de ADN , Electroforesis en Gel de Poliacrilamida , Electrorretinografía , Femenino , Fondo de Ojo , Eliminación de Gen , Humanos , Masculino , Persona de Mediana Edad , Mutación , Linaje , Fenotipo , Retina/patología , Retina/fisiopatologíaRESUMEN
X linked recessive deafness accounts for only 1.7% of all childhood deafness. Only a few of the at least 28 different X linked syndromes associated with hearing impairment have been characterised at the molecular level. In 1960, a large Norwegian family was reported with early onset progressive sensorineural deafness, which was indexed in McKusick as DFN-1, McKusick 304700. No associated symptoms were described at that time. This family has been restudied clinically. Extensive neurological, neurophysiological, neuroradiological, and biochemical, as well as molecular techniques, have been applied to characterise the X linked recessive syndrome. The family history and extensive characterisation of 16 affected males in five generations confirmed the X linked recessive inheritance and the postlingual progressive nature of the sensorineural deafness. Some obligate carrier females showed signs of minor neuropathy and mild hearing impairment. Restudy of the original DFN-1 family showed that the deafness is part of a progressive X linked recessive syndrome, which includes visual disability leading to cortical blindness, dystonia, fractures, and mental deficiency. Linkage analysis indicated that the gene was linked to locus DXS101 in Xq22 with a lod score of 5.37 (zero recombination). Based on lod-1 support interval of the multipoint analysis, the gene is located in a region spanning from 5 cM proximal to 3 cM distal to this locus. As the proteolipid protein gene (PLP) is within this region and mutations have been shown to be associated with non-classical PMD (Pelizaeus-Merzbacher disease), such as complex X linked hereditary spastic paraplegia, PLP may represent a candidate gene for this disorder. This family represents a new syndrome (Mohr-Tranebjaerg syndrome, MTS) and provides significant new information about a new X linked recessive sydromic type of deafness which was previously thought to be isolated deafness.