全外显子测序分析Noonan综合征RAF1基因新发突变

A novel mutation of RAF1 gene of Noonan syndrome: whole exome sequencing analysis

目的应用全外显子测序技术对疑似Noonan综合征(NS)的危重早产儿及其父母进行基因诊断,探讨基因型与临床表型之间的关系。方法收集患儿及其父母的外周血标本及临床资料,应用Agilent Sure Select Human All Exome V5试剂盒进行全基因组外显子捕获,Illumina 550测序仪进行双端高通量测序,Sanger测序验证家系成员以明确突变遗传方式。结果全外显子测序发现NS患儿RAF1基因杂合错义突变c. 770C>T,p. S257L、Sanger测序验证家系成员为新发突变。结合患儿特殊面容、双侧心房及右室增大、中度肺动脉高压(PAH)等临床症状诊断为Noonan综合征。结论应用全外显子测序技术能够快速发现Noonan综合征基因突变,对重症新生儿病例的明确诊断及临床遗传咨询具有重要意义。

Objective To explore the relationship between genotype and clinical phenotype based on gene diagnosis of critically ill premature infants with Noonan syndrome and their parents using whole exome sequencing analysis.Methods The peripheral blood samples and clinical data of premature infants and their parents were collected,Agilent Sure Select Human All Exome V5 kit was used for whole exome selection.Illumina 550 analyzer was used for double-end high-throughput sequencing.Sanger sequencing was used to confirm mutation types.Results Whole exome sequencing discovered a novel mutation of heterozygous missense mutation c.770 C>T,p.S257 L of RAF1 gene,which was confirmed by Sanger sequencing.Considering the clinical symptoms,such as typical dysmorphic face features,bilateral and right ventricular hypertrophy,and moderate pulmonary arterial hypertension(PAH),the infant was diagnosed as Noonan syndrome.Conclusion Whole exome sequencing can find gene mutation of Noonan syndrome rapidly,which may play an important role in definite diagnosis and clinical genetic counseling of critically ill neonates.