摘要目的:对1个淋巴水肿-双行睫综合征(lymphedema-distichiasis syndrome，LDS)家系患者的FOXC2基因进行变异分析，明确患者的致病原因。方法:采集家系成员血液样本并提取DNA和蛋白，对先证者进行全外显子组测序及生物信息学分析，确定可疑致病变异后应用Sanger测序进行家系验证、Western印迹技术检测蛋白表达量的变化。结果:测序结果显示先证者和患病母亲均携带FOXC2基因c.177C>G(p.Tyr59X)杂合无义变异，该变异目前尚未被报道过，Western印迹检测显示FOXC2蛋白表达下降。其母在早孕期B超提示胎儿NT增厚，孕21 ＋1周行羊水穿刺对胎儿进行产前诊断，产前基因诊断结果提示胎儿也携带c.177C>G变异。 结论:FOXC2基因c.177C>G无义变异是患儿的致病原因，并导致Foxc2蛋白表达下降，胎儿NT增厚可能和Foxc2表达量下降有关。本研究结果扩大了FOXC2基因变异谱。

abstractsObjective:To analyze FOXC2 gene variant in a family affected with lymphodema-distichiasis syndrome (LDS).Methods:Peripheral blood samples were collected for the extraction of DNA and protein. Whole-exome sequencing was carried out to detect variants in the proband. Suspected variant was validated by Sanger sequencing. Western blotting was used to detect changes in protein expression.Results:The proband and his mother were both found to carry a heterozygous nonsense variant c. 177C>G(p.Tyr59X) of the FOXC2 gene, which was previously unreported. Down-regulated expression of FOXC2 was detected by Western blotting. Prenatal ultrasonography indicated increased nuchal thickness. Amniocentesis was performed at 21 + 1 weeks of pregnancy, genetic testing suggested that the fetus also carried the c. 177C>G variant. Conclusion:The patients’ condition may be attributed to the heterozygous nonsense variant c. 177C>G of the FOXC2 gene, which resulted in a significant decrease in FOXC2 expression. Increased nuchal thickness may also be related with decreased FOXC2 expression. Above finding has expanded the variant spectrum of the FOXC2 gene.