T. Glaser et al., PAX6 GENE DOSAGE EFFECT IN A FAMILY WITH CONGENITAL CATARACTS, ANIRIDIA, ANOPHTHALMIA AND CENTRAL-NERVOUS-SYSTEM DEFECTS, Nature genetics, 7(4), 1994, pp. 463-471
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 a
nd a milder syndrome consisting of congenital cataracts and late onset
corneal dystrophy. The nonsense mutations, at codons 103 and 353, tru
ncate PAX6 within the N-terminal paired and C-terminal PST domains, re
spectively. The wild-type PST domain activates transcription autonomou
sly 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 mi
ce and suggests a critical role for PAX6 in controlling the migration
and differentiation of specific neuronal progenitor cells in the brain
.