摘要目的:对1个产前肢体畸形合并心脏发育异常胎儿的家系进行研究，明确其遗传学病因，提高对 FANCB基因致病变异导致胎儿多发畸形遗传病因和机制的认识。 方法:选取2021年4月30日于山东省妇幼保健院就诊的1个产前超声提示胎儿发育异常的家系为研究对象。采集该家系相关临床资料，对胎儿进行全外显子组测序(WES)，应用Sanger测序进行家系验证并分析候选变异致病性，对女性成员进行X染色体失活偏倚检测。结果:胎儿孕龄为11 ＋周，产前超声提示脑膜脑膨出、双侧桡骨缺失、唇裂可能、大动脉发育异常及单脐动脉。WES检测提示胎儿携带 FANCB基因c.1162del(p.Y388Tfs*7)半合子变异，Sanger测序验证该变异系母源遗传，根据美国医学遗传学与基因组学学会(ACMG)与ClinGen制订的相关指南，该变异判读为致病性变异(PVS1＋PM2_Supporting＋PP4)。X染色体失活偏倚检测提示孕妇及其母亲的X染色体均完全失活。 结论:FANCB基因c.1162del(p.Y388Tfs*7)半合子变异可能为本研究胎儿肢体畸形合并心脏发育异常的遗传学病因，该基因的致病变异类型与表型之间具有一定的对应关系。

abstractsObjective:To explore the genetic basis for a fetus with limb abnormality and cardiac malformation.Methods:Clinical data of a fetus diagnosed at the Shandong Provincial Maternal and Child Health Care Hospital on April 30th, 2021 was collected. Whole exome sequencing (WES) was carried out, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. X-inactivation analysis was carried out for the female members of its family.Results:The fetus was found to have meningoencephalocele, absence of bilateral radii, cleft lip, abnormal great arteries, and single umbilical artery at the gestational age of 11 + weeks. Sequencing revealed that the fetus has harbored a hemizygous c. 1162del (p.Y388Tfs*7) variant of the FANCB gene, which was maternally inherited. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) and ClinGen, the variant was classified as pathogenic (PVS1+ PM2_Supporting+ PP4). X-inactivation analysis has revealed complete skewed X-inactivation in the pregnant woman and her mother. Conclusion:The hemizygous c. 1162del (p.Y388Tfs*7) variant of the FANCB gene probably underlay the multiple malformations in this fetus.