一个淋巴水肿-双行睫综合征家系的FOXC2基因变异分析

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。

Genetic variant analysis of a pedigree affected with lymphedema-distichiasis syndrome

Objective 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.