McGaughran J M, Oates A, Donnai D, Read A P, Tassabehji M
Queensland Clinical Genetics Service, Royal Children's Hospital and Health District, Herston, Brisbane 4029, Queensland, Australia.
Eur J Hum Genet. 2003 Jun;11(6):468-74. doi: 10.1038/sj.ejhg.5200987.
Pax genes are a highly conserved family of developmental control genes that encode transcription factors. In vertebrates, Pax genes play a role in pattern formation during embryogenesis. Mutations in Pax genes have been associated with both spontaneous mouse mutants and congenital human diseases. The mouse Pax1 mutant phenotype undulated is characterised by vertebral segmentation defects reminiscent of the human disorder Klippel-Feil syndrome (KFS). To determine whether PAX1 haploinsufficiency plays a role in KFS, we have defined the gene structure of the human PAX1 gene and screened 63 KFS patients for mutations in this gene. Differences in the PAX1 sequence were detected in eight patients. Two patients had a silent change within the paired box that was also seen in 2/303 control chromosomes. The other variants were missense, silent or intronic changes not represented in the control panel tested. The significance of these results and the possible role of PAX1 in the pathogenesis of KFS are discussed.
Pax基因是一个高度保守的发育控制基因家族，负责编码转录因子。在脊椎动物中，Pax基因在胚胎发育过程中的模式形成中发挥作用。Pax基因突变与自发的小鼠突变体以及人类先天性疾病均有关联。小鼠Pax1突变体表型“起伏”的特征是脊椎节段缺陷，这使人联想到人类疾病克莱佩尔-费尔综合征（KFS）。为了确定PAX1单倍剂量不足是否在KFS中起作用，我们确定了人类PAX1基因的结构，并对63名KFS患者进行了该基因突变筛查。在8名患者中检测到PAX1序列存在差异。两名患者在配对盒内有一个沉默变化，在2/303条对照染色体中也观察到了该变化。其他变异为错义、沉默或内含子变化，在所检测的对照组中未出现。本文讨论了这些结果的意义以及PAX1在KFS发病机制中的可能作用。
