Genomic structure, evolutionary conservation and aniridia mutations in the human PAX6 gene

• Published in: Nature genetics Vol. 2; no. 3; pp. 232 - 239
• Main Authors: Glaser, Tom, Walton, David S, Maas, Richard L
• Format: Journal Article
• Language: English
• Published: United States 01.11.1992
• Subjects: Amino Acid Sequence; Animals; aniridia; Aniridia - genetics; Base Sequence; cDNA; Chromosome Mapping; Chromosomes, Human, Pair 11; Cloning, Molecular; Conserved Sequence; DNA - metabolism; DNA Mutational Analysis; DNA, Complementary - genetics; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Exons - genetics; Eye Proteins; Female; gene products; genes; Homeodomain Proteins; Humans; Introns - genetics; Male; man; Mice; Molecular Sequence Data; Mutation - genetics; nucleotide sequence; Paired Box Transcription Factors; PAX6 gene; PAX6 Transcription Factor; predictions; Protein Binding; Protein Conformation; Repressor Proteins; Sequence Homology, Amino Acid; Transcription Factors - chemistry; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng1192-232

Aniridia is a semidominant disorder in which development of the iris, lens, cornea and retina is disturbed. The mouse mutation Small eye (Sey), which has been proposed as a model for aniridia, results from defects in Pax-6, a gene containing paired-box and homeobox motifs that is specifically expressed in the developing eye and brain. To test the role of PAX6 in aniridia, we isolated human cDNA clones and determined the intron-exon structure of this gene. PAX6 spans 22 kilobases and is divided into 14 exons. Analysis of DNA from 10 unrelated aniridia patients revealed intragenic mutations in three familial and one sporadic case. These findings indicate that the human aniridia and murine Small eye phenotypes arise from homologous defects in PAX6.