Functional analysis of three genetic disorder related PITX2 mutants

• Published in: Chinese science bulletin 2006, Vol.51 (2), p.164-169
• Main Authors: Wang, Guo, Liu, Xiaoping, Pan, Qian, Liang, Desheng, Wu, Qianling, Dai, Heping, Zhu, Feizhou, Xia, Kun, Xia, Jiahui
• Format: Article
• Language: English
• Subjects: PITX2突变体; 功能分析; 常染色体; 显性等位基因; 遗传性障碍
• ISSN: 1001-6538; 1861-9541
• DOI: 10.1007/s11434-005-1374-4

The autosome dominant disorders, ring dermoid of the cornea （RDC）, iris hypolasia （IH） and Axenfeld-Rieger syndrome （ARS）, are allelic disorders, as all three can result from mutations of the transcriptional factor PITX2. Among three disorder phenotypes, ARS is the most severe, IH is milder than ARS, and RDC is the mUdest. Missense mutations of the PITX2 homeodomain identified in RDC （R62H）, IH （R84W） and ARS patients （T68P） were introduced into PITX2 cDNA by site-directed mutagenesis. PITX2 mutant proteins expressed in eucaryotic cells were stable and localized to the nu- cleus. Analysis of these mutant PITX2 proteins by DNA-binding shift and transactivation studies demonstrated that the R62H had the most activity in both studies, and the R84W still retained somewhat functions, whereas the T68P proved to be non-functional. These results are consistent with previous hypothesis that varying amount of residual PITX2 mutant activity could underline the severity of these phenotypes.