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 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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Abnormalities, Multiple / genetics*
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Amino Acid Sequence
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Animals
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Aniridia / genetics
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Anophthalmos / genetics
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Base Sequence
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Brain / abnormalities*
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Cataract / congenital
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Cataract / genetics
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DNA / genetics
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DNA Mutational Analysis
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DNA Primers / genetics
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DNA-Binding Proteins / genetics*
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Eye Abnormalities / genetics*
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Eye Proteins
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Female
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Homeodomain Proteins*
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Homozygote
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Humans
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Infant, Newborn
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Male
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Mice
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Mice, Mutant Strains
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Molecular Sequence Data
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PAX6 Transcription Factor
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Paired Box Transcription Factors
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Pedigree
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Point Mutation
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Repressor Proteins
Substances
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DNA Primers
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DNA-Binding Proteins
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Eye Proteins
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Homeodomain Proteins
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PAX6 Transcription Factor
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PAX6 protein, human
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Paired Box Transcription Factors
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Pax6 protein, mouse
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Repressor Proteins
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DNA