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Article
Nature Genetics  2, 232 - 239 (1992)
doi:10.1038/ng1192-232

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

Tom Glaser1, David S. Walton2 & Richard L. Maas1

  1Genetics Division, Department of Medicine and Howard Hughes Medical Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA

  2Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts 02114, USA

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.

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