Tassabehji M, Newton V E, Leverton K, Turnbull K, Seemanova E, Kunze J, Sperling K, Strachan T, Read A P
Department of Medical Genetics, St Mary's Hospital, Manchester, UK.
Hum Mol Genet. 1994 Jul;3(7):1069-74. doi: 10.1093/hmg/3.7.1069.
The human PAX3 gene contains a paired box and a paired-type homeobox, and is believed to play a role in pattern formation in the embryo. We describe the exon-intron structure of the homeobox-containing part of PAX3, complementing earlier descriptions of the 5' part of the gene. Mutations in PAX3 have been described in patients with Type 1 Waardenburg syndrome, who have hearing loss and pigmentary abnormalities, while Splotch mice have mutations in the homologous mouse Pax-3 gene. We describe a series of patients who have previously unidentified PAX3 mutations. These include a chromosomal deletion, a splice-site mutation and an amino acid substitution which closely correspond to the molecular changes seen in the Splotch-retarded, Splotch and Splotch-delayed mouse mutants respectively. These mutations confirm that Waardenburg syndrome is produced by gene dosage effects and show that the phenotypic differences between Splotch mice and humans with Waardenburg syndrome are caused by differences in genetic background rather than different primary effects of the mutations.
人类PAX3基因包含一个配对结构域和一个配对型同源异型结构域，据信该基因在胚胎的模式形成中发挥作用。我们描述了PAX3基因含同源异型结构域部分的外显子-内含子结构，补充了该基因5'端部分的早期描述。在患有1型瓦登伯革氏综合征的患者中发现了PAX3基因突变，这些患者有听力损失和色素异常，而斑驳小鼠的同源小鼠Pax-3基因存在突变。我们描述了一系列此前未被识别出PAX3基因突变的患者。这些突变包括一个染色体缺失、一个剪接位点突变和一个氨基酸替换，它们分别与斑驳延迟、斑驳和斑驳迟缓小鼠突变体中观察到的分子变化密切对应。这些突变证实瓦登伯革氏综合征是由基因剂量效应引起的，并且表明斑驳小鼠与患有瓦登伯革氏综合征的人类之间的表型差异是由遗传背景的差异而非突变的不同主要效应导致的。
