PAX6 GENE DOSAGE EFFECT IN A FAMILY WITH CONGENITAL CATARACTS, ANIRIDIA, ANOPHTHALMIA AND CENTRAL-NERVOUS-SYSTEM DEFECTS

Citation
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
Citations number
51
Categorie Soggetti
Genetics & Heredity
Journal title
ISSN journal
10614036
Volume
7
Issue
4
Year of publication
1994
Pages
463 - 471
Database
ISI
SICI code
1061-4036(1994)7:4<463:PGDEIA>2.0.ZU;2-O
Abstract
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 .