一个先天性挛缩蜘蛛指畸形综合征家系的FBN2基因变异分析及产前诊断

目的对1个中国先天性挛缩蜘蛛指畸形综合征(congenital contractural arachnodactyly,CCA)家系进行致病基因分析,明确其致病变异,为家系遗传咨询和产前诊断提供依据。方法应用二代测序技术(骨骼疾病Panel)对先证者进行变异筛查,发现FBN2基因可疑致病位点后,用Sanger测序技术对该家系成员和100名正常对照进行新变异验证,确定该家系的致病位点,并对家系中孕23周胎儿抽取羊水标本进行产前诊断。结果先证者及家系中所有患者均携带FBN2基因c.3528C>A(p.Asn1176Lys)杂合变异,而家系正常成员和100名正常对照中均未检测到该变异。产前诊断结果显示胎儿也携带FBN2基因c.3528C>A(p.Asn1176Lys)杂合变异。结论FBN2基因c.3528C>A(p.Asn1176Lys)变异是该家系的致病原因,新变异的检出丰富了FBN2基因变异谱。

Pathological variant of FBN2 gene identified in a pedigree affected with congenital contracture arachnodactyly

Objective To detect pathological variant in a Chinese pedigree affected with congenital contractural arachnodactyly(CCA).Methods Next generation sequencing(NGS)was used to scan the whole exome of the proband.Potential variant of the FBN2 gene was also detected in all members of the pedigree and 100 healthy controls by Sanger sequencing.With the determination of the genotype,prenatal diagnosis was carried out by amniotic fluid sampling.Results A c.3528C>A(p.Asn1176Lys)variant was identified in the FBN2 gene of the proband,other patients from this pedigree,as well as the fetus.The same variant was not found among healthy members from this pedigree and the 100 healthy controls.Conclusion The c.3528C>A(p.Asn1176Lys)variant of the FBN2 gene probably underlies the pathogenesis of CCA in our case.The new variant has enriched pathological spectrum of the FBN2 gene.