1例马凡综合征患者新发FBN1基因突变分析

doi:10.6040/j.issn.1673-3770.0.2022.207

摘要/Abstract

摘要： 目的通过对1例临床诊断为马凡综合征的患儿进行致病基因测序分析,明确其遗传学病因。方法提取先证者及其父母基因组DNA进行全外显子测序分析,对筛选出的可疑位点应用Sanger测序技术验证,根据ACMG发布的指南评估变异致病性,并利用生物信息学蛋白功能软件进行预测分析。结果全外显子测序分析结果显示,先证者FBN1基因存在c.4016G>T(p.C1339F)杂合错义突变。Sanger测序显示其父母该位点无变异,属于自发突变。根据 ACMG 指南判定为致病性变异。生物信息学蛋白功能预测结果为有害。结论 FBN1基因c.4016G>T(p.C1339F)杂合突变可能是该Marfan 综合征患儿的致病原因,检出的新变异丰富了FBN1基因变异谱。

关键词: 马凡综合征, FBN1基因, 杂合突变, 基因突变, 全外显子测序

Abstract: Objective To identify the genetic etiology, sequencing analysis of the causative gene was performed in a child with a clinical diagnosis of Marfan syndrome. Methods Genomic DNA was extracted from the peripheral blood samples of the proband and his parents for whole exome sequencing analysis; the suspected loci were then verified using Sanger sequencing. The pathogenicity of the variants was assessed according to the guidelines issued by the American College of Medical Genetics and Genomics(ACMG), and predictive analysis was performed using REVEL-a bioinformatics software for the comprehensive prediction of the pathogenicity of missense variants. Results The results of whole exome sequencing analysis showed that the FBN1 gene was associated with the c. 4016G > T(p.C1339F)heterozygous missense mutation in the child. Results of Sanger sequencing showed that his parents had no variation at this locus and exhibited spontaneous mutations. According to the ACMG guidelines, this variant was tentatively determined to be a pathogenic variant. REVEL predicted the missense variant as harmful, and SIFT, PolyPhen 2, Mutation Taster, and GERP + predicted it to be deleterious. Conclusion The c.4016G > T(p.C1339F)heterozygous mutation in the FBN1 gene may be the cause of the disease in our patient with Marfan syndrome; this new variant further expands the FBN1 variant spectrum.

Key words: Marfan syndrome, FBN1 gene, Heterozygous mutation, Genes mutation, Whole exome sequencing

中图分类号:

R596.1

赵爽, 赵军, 薛友余, 张娟美. 1例马凡综合征患者新发FBN1基因突变分析[J]. 山东大学耳鼻喉眼学报, 2023, 37(2): 98-103.

ZHAO Shuang, ZHAO Jun, XUE Youyu, ZHANG Juanmei. Analysis of a new-onset FBN1 gene mutation in a patient with Marfan syndrome[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2023, 37(2): 98-103.

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