FBN1基因新变异所致马凡综合征患儿1例的分析

Analysis of a child with Marfan syndrome due to a novel variant of FBN1 gene

目的探讨1例马凡综合征(MFS)患儿的遗传学病因,并分析其临床表型与基因型的相关性。方法选取2021年3月30日于中南大学湘雅三医院就诊的1例MFS患儿为研究对象。收集患儿及其家系成员的外周血样,提取基因组DNA,进行家系全外显子组测序,对候选致病变异进行Sanger测序家系验证,并用生物信息学软件分析变异的致病性。结果患儿为13岁男性,MFS体型包括身材瘦长、臂展大于身高、手指及足趾细长、漏斗胸、脊柱侧弯,但未见主动脉扩张或胸腹主动脉瘤、二尖瓣脱垂等典型病变,晶状体未见脱位。全外显子组测序显示其FBN1基因存在c.7383_7413del(p.N2461Kfs*211)杂合变异,其父母、弟弟均未发现相同的变异。该变异既往未见文献报道,被判断为致病性。结论本研究发现了FBN1基因的一个新变异,进一步拓展了MFS的变异谱及表型谱。

Objective To carry out genetic testing for a child with Marfan syndrome(MFS)and explore its genotype-phenotype correlation.Methods Peripheral blood samples of the child and his parents were collected for the extraction of genomic DNA and subjected to whole exome sequencing(WES).Candidate variants were verified by Sanger sequencing.Functional impact of the variant was predicted by using bioinformatic software.Results The child,a 13-year-old male,has featured Marfanoid habitus,with arm span exceeding his height,tapering fingers and toes,pectus excavatum and scoliosis,but absence of typical cardiovascular system diseases such as aortic dilation,thoracic-abdominal aortic aneurysm,mitral valve prolapse,and lens dislocation.The child has harbored a novel splice site variant c.7383_7413del(p.N2461Kfs*211)of the FBN1 gene,which was not found in his parents and younger brother.The variant was unreported previously.Conclusion The novel variant of p.N2461Kfs*211 of the FBN1 gene probably underlay the MFS in this child.Above finding has enriched the genotypic and phenotypic spectrum of MFS.