Nishimura D Y, Swiderski R E, Alward W L, Searby C C, Patil S R, Bennet S R, Kanis A B, Gastier J M, Stone E M, Sheffield V C
Department of Pediatrics, University of Iowa, Iowa City 52242, USA.
Nat Genet. 1998 Jun;19(2):140-7. doi: 10.1038/493.
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 (PCG) 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 PCG 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.
许多不同的眼部疾病，其表型包含早发性青光眼，已被定位到人类染色体6p25。这些疾病被推测要么彼此等位，要么与一组紧密连锁的基因相关。我们鉴定出两名患有涉及6p25染色体异常的原发性先天性青光眼（PCG）患者。为了鉴定一个与PCG相关的基因，对一名6p25与13q22之间存在平衡易位患者的染色体断点进行了克隆。6p25断点的克隆基于与断点的接近程度鉴定出两个候选基因。其中一个是FKHL7，编码一个叉头转录因子，它在平衡易位患者中紧邻断点，并且在另一名患有部分6p单体性的PCG患者中缺失。此外，在被诊断患有里格尔异常（RA）、阿克森费尔德异常（AA）和虹膜发育不全（IH）的患者中发现FKHL7存在突变。这项研究表明FKHL7中的突变导致了一系列青光眼表型。
