RESUMO
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.
Assuntos
Degeneração Macular , Miopia , Distrofias Retinianas , Retinose Pigmentar , Transportadores de Cassetes de Ligação de ATP/genética , Atrofia , Análise Mutacional de DNA , Eletrorretinografia , Proteínas do Olho/genética , Humanos , Kuweit/epidemiologia , Degeneração Macular/diagnóstico , Degeneração Macular/genética , Mutação , Linhagem , Fenótipo , Distrofias Retinianas/diagnóstico , Distrofias Retinianas/genética , Retinose Pigmentar/genéticaRESUMO
We studied 21 patients with Sanjad-Sakati syndrome (SSS) from 16 families. Parental consanguinity was recorded in 2 families (12.5%). All patients had severe intrauterine growth retardation, short stature, small hands and feet, blue sclera, deep-set eyes, microcephaly, persistent hypocalcaemia and hypoparathyroidism. Medullary stenosis was detected in 2 patients. Cytogenetic and fluorescent in situ hybridization studies were normal. All affected persons had homozygous deletion of 12 bp (155-166del) in exon 3 of the TBCE gene. All of the parents were heterozygous carriers of this mutation. The high frequency of SSS and low frequency of consanguineous marriages in this study may reflect a high rate of heterozygous carriers.
Assuntos
Anormalidades Múltiplas/genética , Retardo do Crescimento Fetal/genética , Hipocalcemia/genética , Hipoparatireoidismo/genética , Deficiência Intelectual/genética , Microcefalia/genética , Anormalidades Múltiplas/epidemiologia , Deleção Cromossômica , Consanguinidade , Análise Citogenética , Retardo do Crescimento Fetal/epidemiologia , Genes Recessivos/genética , Heterozigoto , Homozigoto , Humanos , Hipocalcemia/epidemiologia , Hipoparatireoidismo/epidemiologia , Hibridização in Situ Fluorescente , Recém-Nascido , Deficiência Intelectual/epidemiologia , Kuweit/epidemiologia , Microcefalia/epidemiologia , Chaperonas Moleculares/genética , Mutação/genética , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , SíndromeRESUMO
We studied 21 patients with Sanjad-Sakati syndrome [SSS] from 16 families. Parental consanguinity was recorded in 2 families [12.5%]. All patients had severe intrauterine growth retardation, short stature, small hands and feet, blue sclera, deep-set eyes, microcephaly, persistent hypocalcaemia and hypoparathyroidism. Medullary stenosis was detected in 2 patients. Cytogenetic and fluorescent in situ hybridization studies were normal. All affected persons had homozygous deletion of 12 bp [155-166del] in exon 3 of the TBCE gene. All of the parents were heterozygous carriers of this mutation. The high frequency of SSS and low frequency of consanguineous marriages in this study may reflect a high rate of heterozygous carriers