RESUMEN
PURPOSE: To determine the frequency of Usher's syndrome and other ocular disease in students receiving special education services for the deaf in Oregon and to assess the amount of existing ophthalmologic surveillance of this population. A special emphasis was placed on screening for Usher's syndrome. METHODS: From 1980-1990, a prospective two-center visual screening program of 231 deaf students in schools throughout Oregon was conducted using an ophthalmic questionnaire, complete eye examinations, and electroretinography. Students were between the ages of 10 and 21 years and participated on a volunteer basis. Findings for etiology and severity of visual loss and the scope of ophthalmologic surveillance within this population were analyzed. RESULTS: Two hundred seventeen of the 231 students examined received electroretinograms. Significant ocular pathology was found in 111 (48%) of the students. The most common diagnoses were congenital rubella (21%), significant uncorrected ametropia (16%), and ocular hypertension (9%). Five students were diagnosed with Usher's syndrome. Of the students with significant ocular pathology, only 37% were actively followed by an ophthalmologist. CONCLUSION: Deaf students in Oregon's schools had a high frequency of eye disease. Early diagnosis and treatment of eye disease in this population could benefit the quality of life of these students. This study alerted the providers of special education services for the deaf and the ophthalmologic community in Oregon of the need for better eye care for these students.
Asunto(s)
Oftalmopatías/epidemiología , Personas con Deficiencia Auditiva/estadística & datos numéricos , Selección Visual , Adolescente , Adulto , Niño , Electrorretinografía , Oftalmopatías/diagnóstico , Humanos , Oregon/epidemiología , Estudios Prospectivos , Calidad de Vida , Instituciones Académicas , Estudiantes , Encuestas y CuestionariosRESUMEN
BACKGROUND: Mutations in the RPGR gene at the RP3 locus have been found to cause x-linked retinitis pigmentosa in some families. OBJECTIVES: To identify a previously undescribed 2-base pair insertion in codon 99 of the RPGR gene and to describe the phenotype in a well-characterized family with X-linked retinitis pigmentosa. DESIGN: Case reports with clinical features, fluorescein angiography, kinetic perimetry, electrophysiological studies, and molecular genetics. SETTING: University medical centers. PATIENTS: Eight members of the family were screened for the codon 99 insertion in the RPGR gene. RESULTS: Three affected males were found to be hemizygous for the 2-base pair insertion; 2 carriers were heterozygous. This insertion creates a frameshift that would be expected to cause a premature arrest of translation after only 132 amino acids (683 amino acids less than the normal protein). The affected males had typical retinitis pigmentosa with visual field contraction and abnormal findings on electroretinograms with little to no rod activity, profoundly subnormal residual cone responses to single flash and 30-Hz flicker stimuli, and prolonged b-wave implicit times. The electroretinogram of a 49-year-old carrier showed amplitudes that were roughly half of normal. Carrier women did not show a tapetallike fundus reflex but showed asymmetrical patchy pigmentary disturbances consistent with lyonization. CONCLUSION: A frameshifting 2-base pair insertion at codon 99 of the RPGR gene produced typical retinitis pigmentosa and carrier findings (but no tapetallike reflex) in this family.
Asunto(s)
Proteínas Portadoras/genética , Codón/genética , Proteínas del Ojo , Ligamiento Genético/genética , Mutagénesis Insercional , Proteínas/genética , Retinitis Pigmentosa/genética , Cromosoma X/genética , Adolescente , Adulto , Análisis Mutacional de ADN , Cartilla de ADN/química , Elementos Transponibles de ADN/genética , Electrorretinografía , Femenino , Angiografía con Fluoresceína , Mutación del Sistema de Lectura , Humanos , Masculino , Persona de Mediana Edad , Linaje , Polimorfismo Conformacional Retorcido-Simple , Retina/patología , Retina/fisiopatología , Retinitis Pigmentosa/patología , Retinitis Pigmentosa/fisiopatología , Agudeza Visual , Pruebas del Campo Visual , Campos VisualesRESUMEN
Sorbsy fundus dystrophy (SFD) is an autosomal dominant disorder that is characterized by bilateral loss of central vision secondary to choroidal neovascularization and/or pigment epithelial atrophy in the macula, with onset of visual symptoms usually in the fourth or fifth decade. Drusenlike changes may occur, with impaired dark adaptation and abnormal electroretinographic results.
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Fondo de Ojo , Degeneración Macular/genética , Mutación Puntual , Proteínas/genética , Adulto , Anciano , Cromosomas Humanos Par 22/genética , Cisteína/genética , ADN/análisis , Femenino , Humanos , Mácula Lútea/patología , Degeneración Macular/enzimología , Degeneración Macular/patología , Masculino , Repeticiones de Microsatélite , Persona de Mediana Edad , Linaje , Serina/genética , Inhibidor Tisular de Metaloproteinasa-3Asunto(s)
Proteínas del Ojo/genética , Proteínas de Filamentos Intermediarios/genética , Glicoproteínas de Membrana , Proteínas de la Membrana/genética , Mutación , Proteínas del Tejido Nervioso , Retinitis Pigmentosa/genética , Femenino , Heterocigoto , Humanos , Masculino , Linaje , Periferinas , Degeneración Retiniana/genética , TetraspaninasRESUMEN
PURPOSE: Dystrophin, the Duchenne muscular dystrophy gene product, has been localized to the outer plexiform layer of normal human retina. The purpose of this study is to define completely the ocular phenotype associated with mutations at Xp21, the Duchenne muscular dystrophy gene locus. METHODS: Twenty-one patients with a diagnosis of Duchenne muscular dystrophy and five patients with Becker muscular dystrophy had ophthalmologic examinations, including electroretinograms (ERGs). Electroretinogram results were correlated with respect to patient DNA analysis. RESULTS: Twenty-three (88%) patients had reduced scotopic b-wave amplitudes to bright-white flash stimulus, including nine with negative-shaped ERGs. Rod-isolated responses were reduced or not recordable above noise in 14 (67%) patients. Most isolated cone responses (92%) were normal. Flicker amplitudes were reduced in seven patients. Two of these patients with proximal (5' end) deletions had normal scotopic b-waves to dim blue and bright-white flash stimulus. Patients with deletions toward the middle of the gene had greater reductions in their scotopic b-wave amplitudes than patients with deletions located toward the 5' end. Most patients had normal color vision, extraocular muscle function, and Snellen visual acuity. Increased macular pigmentation was seen in 16 patients with Duchenne muscular dystrophy. CONCLUSION: Most patients with Duchenne or Becker muscular dystrophy have evidence of abnormal scotopic ERGs. Patients with deletions in the central region of the gene had the most severe ERG changes. This study supports previous suggestions that dystrophin may play a role in retinal neurotransmission. The presence of increased macular pigmentation and normal photopic ERGs distinguishes patients with Duchenne muscular dystrophy mutations from other X-linked retinal disorders with negative-shaped ERGs.
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Distrofias Musculares/fisiopatología , Retina/fisiopatología , Adolescente , Adulto , Niño , Percepción de Color , ADN/análisis , Percepción de Profundidad , Electrorretinografía , Femenino , Fondo de Ojo , Humanos , Luz , Masculino , Persona de Mediana Edad , Distrofias Musculares/genética , Fenotipo , Errores de Refracción/fisiopatología , Visión Binocular , Agudeza VisualRESUMEN
BACKGROUND AND OBJECTIVES: Mutations of the peripherin/RDS gene have been reported in autosomal dominant retinitis pigmentosa, pattern macular dystrophy, and retinitis punctata albescens. We report herein the occurrence of three separate phenotypes within a single family with a novel 3-base pair deletion of codon 153 or 154 of the peripherin/RDS gene. DESIGN: Case reports with clinical features, fluorescein angiography, kinetic perimetry, electrophysiological studies, and molecular genetics. SETTING: University medical centers. PATIENTS: A 75-year-old woman, her two daughters (aged 44 and 50 years), and her 49-year-old son were screened for peripherin/RDS mutations because of the presence of multiple phenotypes within the same family. RESULTS: The mother presented at age 63 years with a profoundly abnormal electroretinogram (ERG) and adult-onset retinitis pigmentosa that progressed dramatically over 12 years, with marked loss of peripheral visual field. One daughter developed pattern macular dystrophy at age 31 years. At age 44 years, her ERG was moderately abnormal but her clinical disease was limited to the macula. Another daughter presented at age 42 years with macular degeneration and over 10 years developed the clinical picture of fundus flavimaculatus. Her peripheral visual field was preserved but her ERG was moderately abnormal. The son had onset of macular degeneration at age 44 years. Pericentral scotomas were present and the ERG was markedly abnormal. Fluorescein angiography revealed punctate pigment epithelial transmission defects. CONCLUSIONS: A 3-base pair deletion of codon 153 or 154 of the peripherin/RDS gene can produce clinically disparate phenotypes even within the same family.
Asunto(s)
Deleción Cromosómica , Codón , Proteínas de Filamentos Intermediarios/genética , Degeneración Macular/genética , Glicoproteínas de Membrana , Proteínas del Tejido Nervioso , Degeneración Retiniana/genética , Retinitis Pigmentosa/genética , Adulto , Anciano , Niño , Análisis Mutacional de ADN , Femenino , Fondo de Ojo , Humanos , Degeneración Macular/patología , Masculino , Persona de Mediana Edad , Linaje , Periferinas , Fenotipo , Mutación Puntual , Degeneración Retiniana/patología , Retinitis Pigmentosa/patología , Campos VisualesRESUMEN
We have studied retinal function by electroretinography in five Becker and six Duchenne muscular dystrophy patients. All had abnormal electroretinograms with a markedly reduced amplitude for the b-wave in the dark-adapted state. Using three antisera raised to different domains of dystrophin, we identified dystrophin in the outer plexiform layer of human retina. The retinal dystrophin is present in multiple isoforms as the result of alternative splicing. The localization of dystrophin to the outer plexiform layer coincident with the abnormal b-wave suggests that dystrophin is required for normal retinal electrophysiology.
Asunto(s)
Distrofina/fisiología , Electrorretinografía , Proteínas del Ojo/fisiología , Distrofias Musculares/fisiopatología , Retina/química , Adolescente , Adulto , Secuencia de Bases , Niño , Distrofina/biosíntesis , Distrofina/genética , Proteínas del Ojo/biosíntesis , Proteínas del Ojo/genética , Humanos , Datos de Secuencia Molecular , Distrofias Musculares/genética , Especificidad de Órganos , Reacción en Cadena de la Polimerasa , ARN Mensajero/análisis , Retina/fisiopatologíaRESUMEN
X-linked congenital stationary night blindness (CSNB) is a nonprogressive retinal disorder characterized by a presumptive defect of neurotransmission between the photoreceptor and bipolar cells. Carriers are not clinically detectable. A new classification for CSNB includes a complete type, which lacks rod function by electroretinography and dark adaptometry, and an incomplete type, which shows some rod function on scotopic testing. The refraction in the complete CSNB patients ranges from mild to severe myopia; the incomplete ranges from moderate hyperopia to moderate myopia. To map the gene responsible for this disease, we studied eight multigeneration families, seven with complete CSNB (CSNB1) and one with incomplete CSNB, by linkage analysis using 17 polymorphic X-chromosome markers. We found tight genetic linkage between CSNB1 and an Xp11.3 DNA polymorphic site, DXS7, in seven families with CSNB1 (LOD 7.35 at theta = 0). No recombinations to CSNB1 were found with marker loci DXS7 and DXS14. The result with DXS14 may be due to the small number of scored meioses (10). No linkage could be shown with Xq loci PGK, DXYS1, DXS52, and DXS15. Pairwise linkage analysis maps the gene for CSNB1 at Xp11.3 and suggests that the CSNB1 locus is distal to another Xp11 marker, TIMP, and proximal to the OTC locus. Five-point analysis on the eight families supported the order DXS7-CSNB1-TIMP-DXS225-DXS14. The odds in favor of this order were 9863:1. Removal of the family with incomplete CSNB (F21) revealed two most favored orders, DXS7-CSNB1-TIMP-DXS255-DXS14 and CSNB1-DXS7-TIMP-DXS255-DXS14. Heterogeneity testing using the CSNB1-M27 beta and CSNB1-TIMP linkage data (DXS7 was not informative in F21) was not significant to support evidence of genetic heterogeneity (P = 0.155 and 0.160, respectively).
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Ligamiento Genético , Ceguera Nocturna/genética , Cromosoma X , Alelos , Mapeo Cromosómico , Femenino , Genotipo , Humanos , Masculino , Ceguera Nocturna/congénito , Linaje , Polimorfismo de Longitud del Fragmento de Restricción , Recombinación GenéticaRESUMEN
Pilot programs for screening of newborn infants for congenital hypothyroidism began in North America in 1972. To date, the five oldest programs (Quebec, Pittsburgh, Toronto, Oregon Regional, and New England Regional) have screened 1,046,362 infants. A total of 277 infants with congenital hypothyroidism have been detected and seven have been missed, resulting in a total of 284 affected infants in the screened population and an overall incidence of one in 3,684 live births. Of the affected infants, 246 were determined to have primary hypothyroidism, an incidence of one in 4,254 births. Ten infants with secondary-tertiary hypothyroidism were detected in Quebec, Oregon, and Toronto, an incidence of one in 68,200 births. Of all the infants with primary hypothyroidism who were adequately studied, 63% were determined to have aplastic or hypoplastic glands, 14% normal or enlarged glands, and 23% ectopic thyroid tissue. The estimated minimum incidence of infants with TBG deficiency is one in 8,913 births. Only 8 of the 277 detected infants were suspected clinically to have congenital hypothyroidism prior to the time of confirmation of the diagnosis at 4 to 8 weeks of age. The cost of screening varied from $0.70 to $1.60 per infant, depending on which costs were included in the estimate. Preliminary evidence from Quebec suggests that infants treated in the program have normal developmental testing scores at 18 months of age.
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Hipotiroidismo Congénito , Tamizaje Masivo , alfa-Globulinas/deficiencia , Humanos , Hipotiroidismo/diagnóstico , Hipotiroidismo/epidemiología , Lactante , Recién Nacido , Tamizaje Masivo/economía , América del Norte , Proteínas de Unión a Tiroxina/deficiencia , Agencias Voluntarias de SaludRESUMEN
The Northwest Regional Screening Program to detect congenital hypothyroidism in infants born in Oregon, Montana, Alaska, and Idaho (combined birthrate of 69,000/ yr) was added to our ongoing screening program in 1975. The program utilizes dried blood filter paper specimens collected routinely in the first few days of life in all four states and again at about 6 weeks of age in Oregon only. The screening test consist of an initial thyroxine (T4) measurement; a thyroid-stimulating hormore (TSH) determination is performed on those specimens with T4 concentrations in the lowest 3% group. Serum samples obtained by venipuncture are requested for confirmation of the diagnosis. In the first two years of the program, 25 infants with primary hypothyroidism were detected amont 110,667 infants screened, a frequency of 1:4,430. Fourteen cases of thyroxine-binding globulin deficiency were also detected, a frequency of 1:7,900. Using the T4 followed by TSH testing approach, the frequency of request for repeat specimens was 0.4% in Oregon and 0.05% in the other states. The cost per specimen was $1.96. The majority of infants lacked clinical signs or symptoms of hypothyroidism; only one infant was clinically suspected of having hypothyroidism prior to detection. The most common neonatal symptoms were constipation, lethargy, and prolonged jaundice, while the most common physical signs were hypotonia, umbilical hernia, and large fontanels. Thyroid scans showed the most common etiology to be thyroid aplasia, followed by an ectopic gland, hypoplasia, and goiter. Serum T4 concentrations were lowest in those infants with aplasia, intermediate in infants with an ectopic gland or hypoplasia, and normal in the infant with the goiter. Neonatal hypothyroidism varies in degree and has several different causes; the capacity to secrete thyroid hormone, the duration before hypothyroidism becomes clinically manifest, and possibly the eventual prognosis for intellectual function depend on the nature of the underlying cause. While the mean age at treatment was 59 days, the goal of diagnosing congenital hypothyroidism and treating affected infants by 1 month of age seems realistic.
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Hipotiroidismo/diagnóstico , Enfermedades del Recién Nacido/diagnóstico , Tamizaje Multifásico , Programas Médicos Regionales , Hormonas Tiroideas/sangre , Hipotiroidismo Congénito , Análisis Costo-Beneficio , Diagnóstico Diferencial , Reacciones Falso Positivas , Femenino , Humanos , Recién Nacido , Masculino , Tamizaje Multifásico/economía , Programas Médicos Regionales/economía , Tirotropina/sangre , Tiroxina/sangre , Triyodotironina/sangre , Estados UnidosRESUMEN
An interesting patient with a deletion of the long arm of chromosome 18 is presented. Her symptoms are severe in comparison with some other 18q--patients, yet she was found to have a mosaicism with a normal 46,XX karyotype in about 20% of her cultured lymphocytes. In addition, she had erythropoietic protoporphyria, was heterozygous for type II or III cystinuria, and had reduced levels of peptidase A activity. Detailed studied on the patient, her family, and two additional 18q--patients suggest that the association with erythropoietic protoporphyria is coincidental and that the cystinuria gene was inherited from the patient's father. The reduced peptidase A activity, however, supports earlier observations that the peptidase A locus maps in the q22 to terminus region of chromosome 18.
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Aberraciones Cromosómicas/complicaciones , Cistinuria/genética , Mosaicismo , Péptido Hidrolasas/metabolismo , Porfirias/genética , Niño , Deleción Cromosómica , Trastornos de los Cromosomas , Cromosomas Humanos 16-18 , Cistinuria/complicaciones , Eritrocitos/enzimología , Femenino , Humanos , Discapacidad Intelectual/genética , Linaje , Péptido Hidrolasas/genética , Porfirias/complicacionesRESUMEN
A simple microfluorometric procedure for the measurement of protoporphyrin in erythrocytes (EPP) is described. The technique, which can be performed in less than 4 minutes with portable equipment, utilizes 40 mul of capillary blood and only one reagent (94 percent acidified ethanol) for the extraction. The results obtained by this micromethod are in close agreement with those of the ethyl acetate/hydrochloric acid double-extraction methods. The EPP concentration increases markedly when the blood lead level is increased, and the test can be used to screen children for lead poisoning. This new micromethod also gives reproducible results when dried blood spots on filter paper are used instead of liquid blood.
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Eritrocitos/análisis , Intoxicación por Plomo/diagnóstico , Porfirinas/sangre , Protoporfirinas/sangre , Fluorometría/métodos , HumanosRESUMEN
Twenty-eight members of one family were investigated for the presence of pulmonary disease concurrent with variable (ZZ, MZ, or MS) degrees of alpha-1 antitrypsin deficiency. Three symptomatic siblings (2, ZZ; 1, MZ) had abnormal pulmonary scans and abnormal routine pulmonary function studies. Five asymptomatic heterozygotes, three of whom had never smoked and were the youngest studied, had distinctly abnormal closing volumes. Three of the five patients also had abnormal perfusion dynamics when scanning was done in the upright position. Pulmonary dysfunction occurs in asymptomatic heterozygotes but requires the use of sensitive techniques for its appreciation.