RESUMEN
PURPOSE: To evaluate the clinical and genetic spectrum of inherited retinal diseases (IRDs) in a Kuwaiti tribe. METHODS: Forty four patients with IRDs from 28 nuclear families from the tribe, were evaluated for presenting symptoms, visual acuity, fundus examination, OCT, microperimetry, full-field (ff), and multifocal electroretinography (mERG) and genotyping. RESULTS: Seventeen patients were diagnosed with autosomal recessive retinitis pigmentosa (arRP) associated with RP1 c.606C>A with onset of nictalopia in the third decade, myopia, and macular atrophy by the age of 50; eleven with autosomal recessive cone/rod dystrophy or macular dystrophy associated with RP1 c.606C>A (p.Asp202Glu) mutation with color and central vision deterioration in teenage, myopia, paracentral ring scotoma and macular atrophy; eleven were with arRP associated with PDE6B c.992 + 1 G > A mutation with onset around 5 years, myopia, cataract, retained central fixation, and ellipsoid zone and late perimacular atrophy; five-with Leber congenital amaurosis associated with homozygous RPGRIP1 for c.1107delA mutation with extinguished ffERG and electrophysiological phenotype of rod and cone; and one patient-with autosomal recessive rod-cone dystrophy associated with homozygous PDE6B c.992 + 1 G > A, who was homozygous ABCA4 c.5882 G > A and heterozygous EYS; c.2137 + 1 G > A. CONCLUSIONS: This study represents a typical tribe from the Middle East with high rate of consanguinity for many generations that harbors multiple mutated genes associated with IRD. It demonstrates the predominant phenotype and its variability in retinal disorders caused by identical mutations and illustrates the nuances in the clinical presentation and disease progression of patients with pathogenic mutations in more than one gene.
Asunto(s)
Degeneración Macular , Miopía , Distrofias Retinianas , Retinitis Pigmentosa , Transportadoras de Casetes de Unión a ATP/genética , Atrofia , Análisis Mutacional de ADN , Electrorretinografía , Proteínas del Ojo/genética , Humanos , Kuwait/epidemiología , Degeneración Macular/diagnóstico , Degeneración Macular/genética , Mutación , Linaje , Fenotipo , Distrofias Retinianas/diagnóstico , Distrofias Retinianas/genética , Retinitis Pigmentosa/genéticaRESUMEN
We investigated major congenital abnormalities in babies born in Al Jahra Hospital, Kuwait from January 2000 to December 2001. Of 7739 live and still births born over this period, 97 babies had major congenital malformations (12.5/1000 births): 49 (50.6%) babies had multiple system malformations, while 48 (49.4%) had single system anomalies. Of the 49 babies with multiple malformations, 21 (42.8%) had recognized syndromes, most of which were autosomal recessive and 17 had chromosomal aberrations. Isolated systems anomalies included central nervous system (12 cases), cardiovascular system (9 cases), skeletal system (7 cases) and gastrointestinal system (6 cases). Of the parents, 68% were consanguineous. Genetic factors were implicated in 79% of cases. Genetic services need to be provided as an effective means for the prevention of these disorders.
Asunto(s)
Anomalías Congénitas/epidemiología , Árabes/genética , Árabes/estadística & datos numéricos , Tasa de Natalidad , Aberraciones Cromosómicas/estadística & datos numéricos , Anomalías Congénitas/diagnóstico , Anomalías Congénitas/genética , Anomalías Congénitas/prevención & control , Consanguinidad , Genes Dominantes/genética , Genes Recesivos/genética , Servicios Genéticos , Pruebas Genéticas , Necesidades y Demandas de Servicios de Salud , Humanos , Incidencia , Recién Nacido , Kuwait/epidemiología , Anamnesis , Herencia Multifactorial/genética , Linaje , Vigilancia de la Población , Diagnóstico Prenatal , Sistema de Registros , Factores de Riesgo , Mortinato/epidemiologíaRESUMEN
We investigated major congenital abnormalities in babies born in Al Jahra Hospital, Kuwait from January 2000 to December 2001. Of 7739 live and still births born over this period, 97 babies had major congenital malformations [12.5/1000 births]: 49 [50.6%] babies had multiple system malformations, while 48 [49.4%] had single system anomalies. Of the 49 babies with multiple malformations, 21 [42.8%] had recognized syndromes, most of which were autosomal recessive and 17 had chromosomal aberrations. Isolated systems anomalies included central nervous system [12 cases], cardiovascular system [9 cases], skeletal system [7 cases] and gastrointestinal system [6 cases]. Of the parents, 68% were consanguineous. Genetic factors were implicated in 79% of cases. Genetic services need to be provided as an effective means for the prevention of these disorders
Asunto(s)
Árabes , Tasa de Natalidad , Aberraciones Cromosómicas , Consanguinidad , Genes Dominantes , Genes Recesivos , Anomalías CongénitasRESUMEN
In a prospective study in Kuwait, 182 mentally retarded male patients who fulfilled 5 or more clinical criteria of fragile X syndrome were screened using polymerase chain reaction (PCR) testing. Twenty patients (11%) were highly suspected of having fragile X syndrome due to mutation at the FRAXA locus; none had mutation at the FRAXE locus. Of these, 11 (55%) were confirmed fragile-X-positive by both cytogenetic and PCR techniques. The most frequent clinical features were: prominent forehead, high arched palate, hyperextensible joints, long ears, prominent jaw, height > 10th centile and attention-deficit hyperactivity. Less common were avoidance of eye contact (45%), autism (45%) and seizures (30%). Large testes were found in 55% of cases. Pre-pubertal and post-pubertal clinical criteria were different.
Asunto(s)
Síndrome del Cromosoma X Frágil/diagnóstico , Síndrome del Cromosoma X Frágil/genética , Discapacidad Intelectual/etiología , Factores de Edad , Southern Blotting , Citogenética/métodos , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil , Síndrome del Cromosoma X Frágil/complicaciones , Síndrome del Cromosoma X Frágil/epidemiología , Pruebas Genéticas/métodos , Humanos , Incidencia , Discapacidad Intelectual/diagnóstico , Kuwait/epidemiología , Masculino , Proteínas del Tejido Nervioso/genética , Linaje , Reacción en Cadena de la Polimerasa/métodos , Prevalencia , Estudios Prospectivos , Pubertad , Proteínas de Unión al ARN/genética , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Factores de Tiempo , Escalas de WechslerRESUMEN
In a prospective study in Kuwait, 182 mentally retarded male patients who fulfilled 5 or more clinical criteria of fragile X syndrome were screened using polymerase chain reaction [PCR] testing. Twenty patients [11%] were highly suspected of having fragile X syndrome due to mutation at the FRAXA locus; none had mutation at the FRAXE locus. Of these, 11 [55%] were confirmed fragile-X-positive by both cytogenetic and PCR techniques. The most frequent clinical features were: prominent forehead, high arched palate, hyperextensible joints, long ears, prominent jaw, height > 10th centile and attention-deficit hyperactivity. Less common were avoidance of eye contact [45%], autism [45%] and seizures [30%]. Large testes were found in 55% of cases. Pre-pubertal and post-pubertal clinical criteria were different