Identification of a novel LFNG variant in a Chinese fetus with spondylocostal dysostosis and a systematic review

IF 2.6 3区生物学 Q2 GENETICS & HEREDITY

Journal of Human Genetics Pub Date : 2024-04-02 DOI:10.1038/s10038-024-01248-3

Lin Wang, Shuji Mizumoto, Ruixue Zhang, Yuqi Zhang, Yuan Liu, Wenjing Cheng, Xin Li, Min Dan, Chunyan Zhang, Xinru Gao, Juan Wang, Jiaqi Han, Lianying Jiao, Yating Wang, Qiujie Jin, Lihui Yang, Chenxing Li, Shuxian Li, Jinhui Zhu, Hai Jiang, Gen Nishimura, Takahiro Yamada, Shuhei Yamada, Na Cai, Rong Qiang, Long Guo

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引用次数: 0

Abstract

Spondylocostal dysostosis (SCDO) encompasses a group of skeletal disorders characterized by multiple segmentation defects in the vertebrae and ribs. SCDO has a complex genetic etiology. This study aimed to analyze and identify pathogenic variants in a fetus with SCDO. Copy number variant sequencing and whole exome sequencing were performed on a Chinese fetus with SCDO, followed by bioinformatics analyses, in vitro functional assays and a systematic review on the reported SCDO cases with LFNG pathogenic variants. Ultrasound examinations in utero exhibited that the fetus had vertebral malformation, scoliosis and tethered cord, but rib malformation was not evident. We found a novel homozygous variant (c.1078 C > T, p.R360C) within the last exon of LFNG. The variant was predicted to cause loss of function of LFNG by in silico prediction tools, which was confirmed by an in vitro assay of LFNG enzyme activity. The systematic review listed a total of 20 variants of LFNG in SCDO. The mutational spectrum spans across all exons of LFNG except the last one. This study reported the first Chinese case of LFNG-related SCDO, revealing the prenatal phenotypes and expanding the mutational spectrum of the disorder.

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在一名患有脊柱骨发育不良症的中国胎儿中鉴定出一种新型 LFNG 变异并进行系统综述

脊柱骨发育不良症（SCDO）是一组以椎骨和肋骨多节段缺损为特征的骨骼疾病。SCDO 的遗传病因复杂。本研究旨在分析和鉴定 SCDO 胎儿的致病变异。研究人员对一名中国 SCDO 胎儿进行了拷贝数变异测序和全外显子测序，随后进行了生物信息学分析、体外功能测试，并对已报道的带有 LFNG 致病变异的 SCDO 病例进行了系统回顾。宫内超声检查显示胎儿有脊椎畸形、脊柱侧弯和脐带系带，但肋骨畸形不明显。我们在LFNG的最后一个外显子中发现了一个新的同源变异体（c.1078 C > T, p.R360C）。体外检测 LFNG 酶的活性证实了这一点。系统综述共列出了20个SCDO患者的LFNG变异体。除最后一个外显子外，变异谱横跨LFNG的所有外显子。本研究报告了中国首例LFNG相关SCDO病例，揭示了该疾病的产前表型，并扩大了该疾病的突变谱。

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来源期刊

Journal of Human Genetics 生物-遗传学

CiteScore

7.20

自引率

0.00%

发文量

101

审稿时长

4-8 weeks

期刊介绍： The Journal of Human Genetics is an international journal publishing articles on human genetics, including medical genetics and human genome analysis. It covers all aspects of human genetics, including molecular genetics, clinical genetics, behavioral genetics, immunogenetics, pharmacogenomics, population genetics, functional genomics, epigenetics, genetic counseling and gene therapy. Articles on the following areas are especially welcome: genetic factors of monogenic and complex disorders, genome-wide association studies, genetic epidemiology, cancer genetics, personal genomics, genotype-phenotype relationships and genome diversity.