A spectrum of FOXC1 mutations suggests gene dosage as a mechanism for developmental defects of the anterior chamber of the eye
A spectrum of FOXC1 mutations suggests gene dosage as a mechanism for developmental defects of the anterior chamber of the eye
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DOI：
10.1086/318183
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发表时间：
2001-02-01
影响因子：
9.8
通讯作者：
Sheffield, VC
中科院分区：
文献类型：
--
作者：
Nishimura, DY;Searby, CC;Sheffield, VC
叉头转录因子基因（FOXC1）的突变已被证明可引起与发育型青光眼相关的眼前房缺陷。这些突变的发现在先天性青光眼患者和涉及6号和13号染色体的平衡易位事件的6p25断点的克隆和表征中得到了极大的促进。在这里，我们描述了在患有眼前房缺陷的患者中FOXC1基因的新突变的鉴定。我们在患有前房眼缺陷的患者中检测到9个新的FOXC1基因突变（其中8个是新的）。在这些突变中，五种移码突变预测叉头结构域的丢失，这是翻译过早终止的结果。特别令人感兴趣的是，两个家庭都有6p25的重复，涉及FOXC1基因。这些数据表明FOXC1单倍体不足和基因剂量增加均可引起眼前房缺损。
Mutations in the forkhead transcription-factor gene (FOXC1), have been shown to cause defects of the anterior chamber of the eye that are associated with developmental forms of glaucoma. Discovery of these mutations was greatly facilitated by the cloning and characterization of the 6p25 breakpoint in a patient with both congenital glaucoma and a balanced-translocation event involving chromosomes 6 and 13. Here we describe the identification of novel mutations in the FOXC1 gene in patients with anterior-chamber defects of the eye. We have detected nine new mutations (eight of which are novel) in the FOXC1 gene in patients with anterior-chamber eye defects. Of these mutations, five frameshift mutations predict loss of the forkhead domain, as a result of premature termination of translation. Of particular interest is the fact that two families have a duplication of 6p25, involving the FOXC1 gene. These data suggest that both FOXC1 haploinsufficiency and increased gene dosage can cause anterior-chamber defects of the eye.