Abstract：
Paired homologous domain transcription factor 2 (PITX2) is critically involved in ocular and cardiac development. Mutations in PITX2 are consistently reported in association with Axenfeld-Rieger syndrome, an autosomal dominant genetic disorder and atrial fibrillation, a common cardiac arrhythmia. In this study, we have mined missense mutations in PITX2 gene from NCBI-dbSNP and Ensembl databases, evaluated the pathogenicity of the missense variants in the homeodomain and C-terminal region using five in silico prediction tools SIFT, PolyPhen2, GERP, Mutation Assessor and CADD. Fifteen homeodomain mutations G42V, G42R, R45W, S49Y, R53W, E53D, E55V, R62H, P65S, R69H, G75R, R84G, R86K, R87W, R91P were found to be highly pathogenic by both SIFT, PolyPhen2 were further functionally characterized using I-Mutant 2.0, Consurf, MutPred and Project Hope. The findings of the study can be used for prioritizing mutations in the context of genetic studies.
摘要：
配对同源域转录因子2（PITX2）与眼部和心脏发育密切相关。PITX2的突变与Axenfeld-Rieger综合征有关，常染色体显性遗传疾病和心房颤动，一种常见的心律失常.在这项研究中,我们从NCBI-dbSNP和Ensembl数据库中挖掘了PITX2基因的错义突变，使用五种模拟预测工具SIFT评估同源结构域和C末端区域中错义变体的致病性，PolyPhen2,GERP,突变评估员和CADD。15个同源结构域突变G42V，G42R,R45W,S49Y,R53W,E53D,E55V,R62H,P65S,R69H,G75R,R84G,R86K,R87W,两种SIFT都发现R91P具有高致病性，使用I-突变体2.0，Consurf，MutPred和希望工程。该研究的结果可用于在遗传研究的背景下优先考虑突变。
