Hydrocephalus and Growth Retardation: A Fetal RNU4ATAC-opathy Missed by Whole-Exome Sequencing.

IF 0.9 4区医学 Q4 GENETICS & HEREDITY Molecular Syndromology Pub Date : 2023-01-01 DOI:10.1159/000524501

Yong-Shan Chen, Jie-Fu He, Tao Quan, Shu-Bin Li, Dong-Zhi Li

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Abstract

Introduction: Whole-exome sequencing (WES) is becoming widely available in prenatal diagnosis. However, as with most scientific methods, WES also has its limitations. The aim of the study was to report a fetal case of RNU4ATAC-opathy which was missed by prenatal WES.

Case presentation: A 28-year-old healthy primigravida was revealed by ultrasound at 20 + 3 weeks of gestation to have a fetus with ventriculomegaly (left 15.1 mm/right 11.9 mm), hypoplastic vermis, and mild growth retardation. Chromosomal microarray analysis and trio WES failed to detect a pathogenic copy number variation and sequence variant. A repeat ultrasound at 23 + 3 weeks showed worsened growth delay and hydrocephalus (left 20.3 mm/right 11.0 mm) with vermis hypoplasia and agenesis of corpus callosum. Further study with whole-genome sequencing (WGS) detected 2 missense mutations of the noncoding RNU4ATAC (NR_023343.1) gene, n.51G>A (rs188343279) and n.16G>A (rs750325275), in the fetus, which were inherited from the father and mother, respectively.

Discussion: Our study highlights the limitation of WES. WGS might be a clinical option for patients who have a structurally abnormal fetus tested negative by WES.

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脑积水和生长迟缓:全外显子组测序遗漏的胎儿rnu4atac病变。

全外显子组测序(WES)在产前诊断中的应用越来越广泛。然而，与大多数科学方法一样，WES也有其局限性。本研究的目的是报告一例产前WES未发现的rnu4atac -病变胎儿病例。病例介绍:一名28岁的健康初产妇，孕20 + 3周超声检查发现胎儿脑室肿大(左15.1 mm/右11.9 mm)，蚓部发育不全，轻度发育迟缓。染色体微阵列分析和三重WES未能检测到致病性拷贝数变异和序列变异。23 + 3周复查超声显示生长迟缓加重，脑积水(左20.3 mm/右11.0 mm)，蚓部发育不全，胼胝体发育不全。通过全基因组测序(WGS)进一步研究，在胎儿中检测到非编码RNU4ATAC (NR_023343.1)基因的2个错义突变，分别为n.51G>A (rs188343279)和n.16G>A (rs750325275)，分别遗传自父亲和母亲。讨论:我们的研究突出了WES的局限性。对于结构异常胎儿经WES检测呈阴性的患者，WGS可能是一种临床选择。

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来源期刊

Molecular Syndromology Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

1.70

自引率

9.10%

发文量

期刊介绍： ''Molecular Syndromology'' publishes high-quality research articles, short reports and reviews on common and rare genetic syndromes, aiming to increase clinical understanding through molecular insights. Topics of particular interest are the molecular basis of genetic syndromes, genotype-phenotype correlation, natural history, strategies in disease management and novel therapeutic approaches based on molecular findings. Research on model systems is also welcome, especially when it is obviously relevant to human genetics. With high-quality reviews on current topics the journal aims to facilitate translation of research findings to a clinical setting while also stimulating further research on clinically relevant questions. The journal targets not only medical geneticists and basic biomedical researchers, but also clinicians dealing with genetic syndromes. With four Associate Editors from three continents and a broad international Editorial Board the journal welcomes submissions covering the latest research from around the world.