Hjalt Tord A, Semina Elena V
Lund University, Department of Experimental Medical Research, BMC B12, Tornavägen 10, SE-22184 Lund, Sweden.
Expert Rev Mol Med. 2005 Nov 8;7(25):1-17. doi: 10.1017/S1462399405010082.
Axenfeld-Rieger syndrome (ARS) is a rare autosomal dominant inherited disorder affecting the development of the eyes, teeth and abdomen. The syndrome is characterised by complete penetrance but variable expressivity. The ocular component of the ARS phenotype has acquired most clinical attention and has been dissected into a spectrum of developmental eye disorders, of which open-angle glaucoma represents the main challenge in terms of treatment. Mutations in several chromosomal loci have been implicated in ARS, including PITX2, FOXC1 and PAX6. Full-spectrum ARS is caused primarily by mutations in the PITX2 gene. The homeobox transcription factor PITX2 is produced as at least four different transcriptional and splicing isoforms, with different biological properties. Intriguingly, PITX2 is also involved in left-right polarity determination, although asymmetry defects are not a feature of ARS. In experimental animal models and in cell culture experiments using PITX2, abundant evidence indicates that a narrow window of expression level of this gene is vital for its correct function.
阿克森费尔德-里格尔综合征（ARS）是一种罕见的常染色体显性遗传性疾病，会影响眼睛、牙齿和腹部的发育。该综合征的特点是完全外显但表现度可变。ARS表型的眼部症状受到了最多的临床关注，并已被细分为一系列发育性眼部疾病，其中开角型青光眼是治疗方面的主要挑战。几个染色体位点的突变与ARS有关，包括PITX2、FOXC1和PAX6。全谱ARS主要由PITX2基因突变引起。同源框转录因子PITX2至少以四种不同的转录和剪接异构体形式产生，具有不同的生物学特性。有趣的是，PITX2也参与左右极性的确定，尽管不对称缺陷不是ARS的特征。在实验动物模型和使用PITX2的细胞培养实验中，大量证据表明该基因的表达水平存在一个狭窄的窗口，这对其正确功能至关重要。
