The forkhead transcription factor gene FKHL7 is responsible for glaucoma phenotypes which map to 6p25
The forkhead transcription factor gene FKHL7 is responsible for glaucoma phenotypes which map to 6p25
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DOI：
10.1038/493
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发表时间：
1998-06-01
期刊：
影响因子：
30.8
通讯作者：
Sheffield, VC
中科院分区：
文献类型：
--
作者：
Nishimura, DY;Swiderski, RE;Sheffield, VC
许多不同的眼部疾病与早发性青光眼的存在作为一个组成部分的表型已被映射到人类染色体6p25。这些疾病被认为是等位基因或与一组紧密连锁的基因有关。我们已经确定了两个原发性先天性青光眼（PCC）患者的染色体异常涉及6p25。为了鉴定与PCG有关的基因，克隆了一个6p25和13q22之间平衡易位的患者的染色体断裂点。6p25断裂点的克隆导致基于与断裂点的接近性鉴定两个候选基因。其中之一，FKHL7，编码叉头转录因子，是在平衡易位患者的断点附近，并在第二个PCC患者部分6p单体性缺失。此外，发现FKHL7在诊断为Rieger异常（RA）、Axenfeld异常（AA）和虹膜发育不全（IH）的患者中具有突变。这项研究表明，FKHL7的突变导致青光眼表型谱。
A number of different eye disorders with the presence of early-onset glaucoma as a component of the phenotype have been mapped to human chromosome 6p25. These disorders have been postulated to be either allelic to each other or associated with a cluster of tightly linked genes. We have identified two primary congenital glaucoma (PCC) patients with chromosomal anomalies involving 6p25. In order to identify a gene involved in PCG, the chromosomal breakpoints in a patient with a balanced translocation between 6p25 and 13q22 were cloned. Cloning of the 6p25 breakpoint led to the identification of two candidate genes based on proximity to the breakpoint. One of these, FKHL7, encoding a forkhead transcription factor, is in close proximity to the breakpoint in the balanced translocation patient and is deleted in a second PCC patient with partial 6p monosomy. Furthermore, FKHL7 was found to harbour mutations in patients diagnosed with Rieger anomaly (RA), Axenfeld anomaly (AA) and iris hypoplasia (IH). This study demonstrates that mutations in FKHL7 cause a spectrum of glaucoma phenotypes.