RESUMO
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.
Assuntos
Proteínas de Ligação a DNA/genética , Genes Homeobox , Fatores de Transcrição/genética , Anormalidades Múltiplas/genética , Alelos , Bacteriófago lambda/genética , Sequência de Bases , Clonagem Molecular , Coloboma/genética , Repetições de Dinucleotídeos , Éxons/genética , Humanos , Rim/anormalidades , Dados de Sequência Molecular , Nervo Óptico/anormalidades , Fator de Transcrição PAX2Assuntos
Coloboma/genética , Proteínas de Ligação a DNA/genética , Nefropatias/genética , Mutação , Nervo Óptico/anormalidades , Epitélio Pigmentado Ocular/anormalidades , Fatores de Transcrição/genética , Proteínas de Ligação a DNA/metabolismo , Feminino , Humanos , Masculino , Fator de Transcrição PAX2 , Síndrome , Fatores de Transcrição/metabolismoRESUMO
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.