Clinical characteristics and genetic analysis of a fetus with Melnick-Needles syndrome due to variant ofFLNA gene
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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+PM2_Supporting+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 theFLNA 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 theFLNA 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.
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 theFLNA 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 theFLNA 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.
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