Abstract：
OBJECTIVE: To explore the clinical features and genetic basis for a fetus featuring Rhizomelic skeletal dysplasia.
METHODS: A fetus diagnosed at the Reproductive and Genetic Center of Suzhou Municipal Hospital in November 2020 was selected as the study subject. Whole exome sequencing (WES) was carried out for the fetus and its parents. Candidate variants were verified by Sanger sequencing. Peripheral blood smears of both parents were also examined.
RESULTS: The fetus was found to have a small chest and short limbs, which had suggested skeletal dysplasia. Genetic testing revealed that the fetus has harbored compound heterozygous variants of the LBR gene, including a paternally derived c.1687+1G>A and a maternally derived c.1757G>A (p.Arg586His). The blood smear of the father showed Pelger-Huet anomaly with hyposegmentation of neutrophil nuclei, while the neutrophils of the mother appeared to be normal. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP), the c.1757G>A (p.Arg586His) variant was classified as likely pathogenic (PM3_Strong+PM2_Supporting+PP3), and so was the c.1687+1G>A variant (PVS1-Moderate+PM3+PM2-Supporting+PP4).
CONCLUSIONS: The compound heterozygous variants of the LBR gene probably underlay the pathogenesis of skeletal dysplasia in this fetus.
METHODS: A fetus diagnosed at the Reproductive and Genetic Center of Suzhou Municipal Hospital in November 2020 was selected as the study subject. Whole exome sequencing (WES) was carried out for the fetus and its parents. Candidate variants were verified by Sanger sequencing. Peripheral blood smears of both parents were also examined.
RESULTS: The fetus was found to have a small chest and short limbs, which had suggested skeletal dysplasia. Genetic testing revealed that the fetus has harbored compound heterozygous variants of the LBR gene, including a paternally derived c.1687+1G>A and a maternally derived c.1757G>A (p.Arg586His). The blood smear of the father showed Pelger-Huet anomaly with hyposegmentation of neutrophil nuclei, while the neutrophils of the mother appeared to be normal. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP), the c.1757G>A (p.Arg586His) variant was classified as likely pathogenic (PM3_Strong+PM2_Supporting+PP3), and so was the c.1687+1G>A variant (PVS1-Moderate+PM3+PM2-Supporting+PP4).
CONCLUSIONS: The compound heterozygous variants of the LBR gene probably underlay the pathogenesis of skeletal dysplasia in this fetus.
摘要：
目的：探讨一例以根佐树骨发育不良为特征的胎儿的临床特征和遗传基础。
方法：选取2020年11月在苏州市医院生殖遗传中心确诊的胎儿作为研究对象。对胎儿及其父母进行全外显子组测序(WES)。通过Sanger测序验证候选变体。还检查了父母双方的外周血涂片。
结果：发现胎儿胸部小，四肢短，这表明骨骼发育不良。基因检测显示，胎儿携带了LBR基因的复合杂合变体，包括父系衍生的c.1687+1G>A和母系衍生的c.1757G>A（p。Arg586His）。父亲的血液涂片显示Pelger-Huet异常，中性粒细胞核缺核，而母亲的中性粒细胞似乎正常。根据美国医学遗传学和基因组学学院（ACMG）和分子病理学协会（AMP）的指南，c.1757G>A（p。Arg586His)变异体被分类为可能致病(PM3_Strong+PM2_Supporting+PP3),c.1687+1G>A变体(PVS1-中等+PM3+PM2-支持+PP4)也是如此。
结论：LBR基因的复合杂合变体可能是该胎儿骨骼发育不良的发病机制。
方法：选取2020年11月在苏州市医院生殖遗传中心确诊的胎儿作为研究对象。对胎儿及其父母进行全外显子组测序(WES)。通过Sanger测序验证候选变体。还检查了父母双方的外周血涂片。
结果：发现胎儿胸部小，四肢短，这表明骨骼发育不良。基因检测显示，胎儿携带了LBR基因的复合杂合变体，包括父系衍生的c.1687+1G>A和母系衍生的c.1757G>A（p。Arg586His）。父亲的血液涂片显示Pelger-Huet异常，中性粒细胞核缺核，而母亲的中性粒细胞似乎正常。根据美国医学遗传学和基因组学学院（ACMG）和分子病理学协会（AMP）的指南，c.1757G>A（p。Arg586His)变异体被分类为可能致病(PM3_Strong+PM2_Supporting+PP3),c.1687+1G>A变体(PVS1-中等+PM3+PM2-支持+PP4)也是如此。
结论：LBR基因的复合杂合变体可能是该胎儿骨骼发育不良的发病机制。
