GLI3基因与单纯性马蹄内翻足的关联分析及其突变筛查

目的对GLU基因与单纯性马蹄内翻足进行关联分析和突变筛查，探讨GLU基因与单纯性马蹄内翻足的相关性。方法应用限制性片段长度多态性分析技术，分析84个单纯性马蹄内翻足核心家系中GLI3基因内两个单核苷酸多态（single nucleotide polymorphisms, SNP）位点的基因型，并应用ETDT软伯统计分析各SNP位点基因型与单纯性马蹄内翻足的关联；应用变性梯度凝胶电泳技术对103例单纯性马蹄内翻足患者GLI3基因的第9至12外显子进行突变筛查。结果经ETDT分析，位于GLI3基因第4外显子的cSNP rs846266差异无统计学意义（χ^2=3．3582，P〉0．05）；第14外显子的cSNP rs929387差异有统计学意义（χ^2=7．2466，P〈0．05），在单纯性马蹄内翻足核心家系中存在传递不平衡；发现1例患者及其母亲的第9外显子有108（G→A）的同义点突变。结论GLI3基因与单纯性马蹄内翻足相关，其第9至12外显子可能并非该病的突变热点。

Association and mutation analysis of GLI3 gene in idiopathic congenital talipes equinovarus

Objective To explore the association and mutation of GLI3 gene in idiopathic congenital talipes equinovarus(ICTEV). Methods 1) Genotype of 2 single nucleotide polymorphism (SNP) in 84 idiopathic congenital talipes equinovarus nuclear pedigree were analyzed by restriction fragment length polymorphism. Association analysis was directed between single SNP locus and ICTEV through ETDT software, respectively.(2) Mutation sites in exon 9,10,11,12 of GLI3 gene were detected in 103 patients with ICTEV by denaturing gradient gel electrophoresis technique. Results rs929387 located in exon 14 of GLI3 gene have transmission disequilibrium in 84 nuclear pedigrees (P<0.05), and rs846266 located in exon 4 have no transmission disequilibrium (P>0.05). A synonymous mutation in exon 9 was detected in one patient and his mother. Conclusion There is an association between GLI3 gene and ICTEV, and exons 9,10,11,12 are not its mutation hot spots.