马凡综合征新发变异一例

A de novo mutation leading to Marfan syndrome in a case

目的对1例不明原因生长发育过快及心脏畸形的患儿进行临床表型及遗传学病因分析。方法对先证者进行全外显子测序分析,应用Sanger测序技术对全外显子筛出的可疑致病基因的变异位点进行验证,并利用生物信息学软件进行功能预测分析。结果全外显子测序结果显示,先证者在FBN1基因的第48外显子上存在c.5846_5848delATA(p.N1949del)缺失变异,Sanger结果显示,其双亲正常,属于新发变异,经Mutation Taster软件预测,该变异具有致病性,结合临床表型确诊为马凡综合征。结论本研究结果增加了中国人马凡综合征人群数据库,同时也扩展了马凡综合征的变异谱;全外显子测序有助于罕见病的研究。

Objective To explore the genetic basis for a child featuring unexplained rapid growth and heart malformation.Methods Whole exome sequencing(WES)was carried out for the patient.Suspected variant was verified by Sanger sequencing and subjected to bioinformatic analysis.Results The child was found to harbor a novel de novo c.5846_5848delATA(p.N1949del)variant in exon 48 of the FBN1 gene,which was predict to be pathogenic by Mutation Taster.The patient was ultimately diagnosed with Marfan syndrome.Conclusion Above finding has enriched the spectrum of genetic variants associated with Marfan syndrome.WES has provided a powerful tool for the diagnosis of rare diseases.