摘要目的:探讨1例肢根型骨发育不良(SD)胎儿的临床表型并分析其遗传学病因。方法:选取2020年11月在苏州市立医院生殖与遗传中心引产的1例胎儿作为研究对象。对胎儿及其父母进行全外显子组测序(WES)，对候选变异进行Sanger测序家系验证，同时对其父母进行外周血细胞形态学检查。结果:胎儿胸廓偏小、四肢短小，考虑为SD。测序发现其存在 LBR基因的复合杂合变异，分别为母源性的c.1757G>A(p.Arg586His)以及父源性的c.1687＋1G>A。胎儿父亲的外周血中性粒细胞存在Pelger-Huёt异常，其母亲中性粒细胞分叶正常。根据美国医学遗传学与基因组学学会相关指南，c.1757G>A(p.Arg586His)被判定为可能致病性变异(PM3_Strong＋PM2_Supporting＋PP3)，c.1687＋1G>A亦被判定为可能致病性变异(PVS1-Moderate＋PM3＋PM2-Supporting＋PP4)。 结论:LBR基因的c.1687＋1G>A和c.1757G>A(p.Arg586His)复合杂合变异考虑为该SD胎儿表现为胸廓偏小、四肢短小的遗传学病因。

abstractsObjective: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-Huёt 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). Conclusion:The compound heterozygous variants of the LBR gene probably underlay the pathogenesis of skeletal dysplasia in this fetus.