Glaser T, Jepeal L, Edwards J G, Young S R, Favor J, Maas R L
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
Nat Genet. 1994 Aug;7(4):463-71. doi: 10.1038/ng0894-463.
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.
人类眼部畸形无虹膜症是由PAX6基因单倍剂量不足引起的，PAX6是一种含有配对结构域的DNA结合蛋白。为了研究这种剂量效应，我们在一个患有无虹膜症以及一种由先天性白内障和迟发性角膜营养不良组成的较轻综合征的家系中，对两个PAX6突变进行了特征分析。这两个无义突变分别位于第103和353密码子，分别在N端配对结构域和C端PST结构域内截断PAX6。野生型PST结构域可自主激活转录，而突变形式具有部分活性。一名复合杂合子患者有严重的颅面和中枢神经系统缺陷且没有眼睛。畸形模式与纯合Sey小鼠相似，提示PAX6在控制大脑中特定神经祖细胞的迁移和分化中起关键作用。
