Nature Genetics
7, 463 - 471 (1994)
doi:10.1038/ng0894-463
PAX6 gene dosage effect in a family with congenital cataracts, aniridia, anophthalmia and central nervous system defectsTom Glaser1, Lisa Jepeal1, Janice G. Edwards2, S. Robert Young2, Jack Favor3
& Richard L. Maas1, 4
1Genetics Division, Department of Medicine and Howard Hughes Medical Institute, Brigham and Women's Hospital Harvard Medical School, Boston, Massachusetts 02115, USA
2Division of Medical Genetics, Department of Obstetrics and Gynecology, University of South Carolina School of Medicine, Columbia, South Carolina 29203, USA
3Institut für Säugetiergenetik, GSF-Forschungzentrum für Umwelt und Gesundheit, D-85758 Oberschlei heim, Germany
4Correspondence should be addressed to R.L.M. The human eye malformation aniridia results from haploinsufficiency of PAX6, a paired box DNA−binding protein. To study this dosage effect, we characterized two PAX6 mutations in a family segregating aniridia and a milder syndrome consisting of congenital cataracts and late onset corneal dystrophy. The nonsense mutations, at codons 103 and 353, truncate PAX6 within the N−terminal paired and C−terminal PST domains, respectively. The wild−type PST domain activates transcription autonomously and the mutant form has partial activity. A compound heterozygote had severe craniofacial and central nervous system defects and no eyes. The pattern of malformations is similar to that in homozygous Sey mice and suggests a critical role for PAX6 in controlling the migration and differentiation of specific neuronal progenitor cells in the brain.
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