FLNA基因变异所致Melnick-Needles综合征胎儿1例的临床特征及遗传学分析  

Clinical characteristics and genetic analysis of a fetus with Melnick-Needles syndrome due to variant of FLNA gene

作　　者：邹竞慧 张宜生 刘燕 薛爱娇 闫露露[2] 李海波 Zou Jinghui;Zhang Yisheng;Liu Yan;Xue Aijiao;Yan Lulu;Li Haibo(Department of Obstetrics,Ningbo Medical Center Lihuili Hospital,Ningbo,Zhejiang 315046,China;the Central Laboratory for Birth Defect Prevention and Control,Ningbo Women and Children′s Hospital,Ningbo,Zhejiang 315012,China)

机构地区：[1]宁波市医疗中心李惠利医院产科,宁波315046 [2]宁波市妇女儿童医院出生缺陷综合防治中心,宁波315012

出　　处：《中华医学遗传学杂志》2023年第5期582-587,共6页Chinese Journal of Medical Genetics

基　　金：浙江省医药卫生计划(2021KY1038、2020KY890);宁波市科技计划(202002N3150)。

摘　　要：目的探讨1例Melnick-Needles综合征(MNS)胎儿的临床及遗传学特征。方法选取2020年11月至宁波市妇女儿童医院确诊的1例MNS胎儿为研究对象。采集胎儿的临床资料,应用家系全外显子组测序(trio-WES)对胎儿及其父母进行致病性变异筛选,对候选变异进行Sanger测序家系验证。结果产前超声提示胎儿偏小、双侧股骨弯曲、脐膨出、单脐动脉,合并羊水过少。Trio-WES发现其携带FLNA基因c.3562G>A(p.A1188T)半合子错义变异,Sanger测序验证为母源性,胎儿父亲该位点为野生型。根据美国医学遗传学与基因组学学会(ACMG)相关指南,评估为可能致病性变异(PS4+PM2Supporting+PP3+PP4)。结论FLNA基因c.3562G>A(p.A1188T)半合子变异可能为该MNS胎儿的遗传学病因。基因诊断有助于MNS的精准诊断,可为家系遗传咨询和再生育提供依据。Objective To explore the clinical and genetic characteristics of a fetus with Melnick-Needles syndrome(MNS).Methods A fetus with MNS diagnosed at Ningbo Women and Children′s Hospital in November 2020 was selected as the study subject.Clinical data was collected.Pathogenic variant was screened by using trio-whole exome sequencing(trio-WES).Candidate variant was verified by Sanger sequencing.Results Prenatal ultrasonography of the fetus had shown multiple anomalies including intrauterine growth retardation,bilateral femur curvature,omphalocele,single umbilical artery,and oligohydramnios.Trio-WES revealed that the fetus has harbored hemizygous c.3562G>A(p.A1188T)missense variant of the FLNA gene.Sanger sequencing confirmed that the variant was maternally derived,whilst its father was of a wild type.Based on the guidelines from the American College of Medical Genetics and Genomics(ACMG),the variant was predicted to be likely pathogenic(PS4+PM2_Supporting+PP3+PP4).Conclusion The hemizygous c.3562G>A(p.A1188T)variant of the FLNA gene probably underlay the structural abnormalities in this fetus.Genetic testing can facilitate accurate diagnosis of MNS and provide a basis for genetic counseling for this family.

关 键 词：Melnick-Needles综合征 FLNA基因 全外显子组测序 错义变异 胎儿 

分 类 号：R714.5[医药卫生—妇产科学]