RESUMEN
Paired box (PAX) genes play a critical role in human development and disease. The PAX2 gene is expressed in primitive cells of the kidney, ureter, eye, ear and central nervous system. We have conducted a mutational analysis of PAX2 in a family with optic nerve colobomas, renal hypoplasia, mild proteinuria and vesicoureteral reflux. We report a single nucleotide deletion in exon five, causing a frame-shift of the PAX2 coding region in the octapeptide domain. The phenotype resulting from the PAX2 mutation in this family was very similar to abnormalities that have been reported in Krd mutant mice. These data suggest that PAX2 is required for normal kidney and eye development.
Asunto(s)
Anomalías Múltiples/genética , Coloboma/genética , Mutación del Sistema de Lectura , Riñón/anomalías , Nervio Óptico/anomalías , Reflujo Vesicoureteral/genética , Adolescente , Adulto , Animales , Secuencia de Bases , Niño , Mapeo Cromosómico , ADN/genética , Proteínas de Unión al ADN/genética , Exones , Femenino , Genes Dominantes , Humanos , Masculino , Ratones , Ratones Mutantes , Datos de Secuencia Molecular , Factor de Transcripción PAX2 , Linaje , Factores de Transcripción/genéticaAsunto(s)
Antígenos de Superficie de la Hepatitis B/aislamiento & purificación , Hepatitis B/inmunología , Adolescente , Adulto , Animales , Bovinos , Niño , Contrainmunoelectroforesis , Estudios Transversales , Perros , Femenino , Sangre Fetal/inmunología , Hepatitis B/epidemiología , Anticuerpos contra la Hepatitis B/análisis , Humanos , Recién Nacido , Masculino , Embarazo , Porcinos , TailandiaRESUMEN
PAX2 is one of nine PAX genes that have been described in vertebrates. Each PAX gene contains a conserved paired box domain that was first identified in Drosophila. PAX2 encodes a transcription factor that has a critical role in the development of the urogenital tract, the eyes, and the CNS. Recently, we reported a mutation of PAX2 in patients with optic nerve coloboma, vesicoureteric reflux, and renal anomalies. To facilitate further analysis of PAX2 mutations in human disease, we have now determined the complete structure of the human PAX2 gene. Five genomic lambda clones containing human PAX2 gene sequences were isolated. Sequencing and restriction mapping of these clones showed that human PAX2 was composed of 12 exons spanning approximately 70 kb. Two alternatively spliced exons and a dinuclotide repeat polymorphism were also determined in PAX2. These data will be useful in characterizing the role of PAX2 in human disease.