DLX3基因罕见变异与发育性髋关节发育不良

目的:筛查DLX3基因(NM_005220)中发育性髋关节发育不良(DDH)相关的致病变异。方法:本研究对192例DDH患者和188例健康对照组的DLX3基因全部外显子区进行Sanger测序,排除已知高频单核苷酸多态性(SNP)位点(最小等位基因频率MAF≥1%)和对照组中存在的变异位点,结合功能性预测和保守性分析,最终筛选出DDH候选致病变异。结果:经过分析,最终在一个DDH患者中筛选出一个错义杂合变异DLX3c.G736C:p.D246H(rs3744539)可能为其致病突变,此变异在物种进化过程中高度保守且致病的可能性较高。结论:本研究首次对DLX3整个外显子区进行变异筛查,并发现新的DDH候选致病变异p.D246H。

Rare variant of DLX3 gene and developmental dysplasia of the hip

Objective:To screen pathogenic variants associated with developmental hip dysplasia (DDH) in the DLX3 gene.Methods:192 patients with DDH and 188 healthy research objects were recruited in this study.All exons coding of DLX3 of the included objects were amplified and sanger sequenced.The known high frequency SNPs (minimum allele frequency≥1％) and variation locus carried by healthy research objects were excluded,and the candidate pathogenic variant of DDH was selected ultimately through functional prediction combined with conservative analysis.Results:A heterozygous missense variant c.G736C:p.D246H (rs3744539) was identified in a patient and it was absent in healthy research objects.This variant was highly conserved in evolution of species and was predicted to be deleterious to the function of DLX3 protein.Conclusion:It is the first time to screen the entire exon region of DLX3 and to found a new DDH candidate pathogenic variant p.D246H.