Prenatal Diagnosis Center, Hangzhou Maternity and Child Care Hospital, 369 Kunpeng Road, Shangcheng District, Hangzhou, 310008, Zhejiang, China.
Department of Cell Biology and Medical Genetics, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Mol Genet Genomics. 2022 Jul;297(4):1017-1026. doi: 10.1007/s00438-022-01899-x. Epub 2022 May 18.
Whole exome sequencing (WES) could yield diagnostic significance in the prenatal diagnosis of skeletal abnormalities. But the phenotypes of fetuses with skeletal abnormalities are heterogenous, and the clinical information we could obtain from an ongoing pregnancy is limited, making the prenatal diagnosis complicated. Therefore, the following interpretation and genetic counseling remain a challenge for clinicians. The aim of this study is to present and investigate the utility of trio-based WES in five fetuses with skeletal anomalies. Five trios with fetal ultrasonic skeletal anomalies were recruited in our study. Fetal specimens and parental peripheral blood were subjected to WES. The fetal skeletal abnormalities were presented through ultrasound scanning images. Fetal WES results showed variants in the PPIB, CHST3, COL1A1, and FGFR3 genes in the five trios. Inherited variants were found in two of the trios, while de novo variants were observed in three of them. Two novel compound heterozygous variants (c.437C > A and c.1044C > G) in CHST3 were identified. We presented five trios with fetal skeletal anomalies, found two novel variants and broadened the spectrum of variants associated with skeletal abnormalities, which would help the establishment of genotype-phenotype relationship in the prenatal setting. Trio-based WES could assist the prenatal diagnosis and genetic counseling of fetuses with skeletal abnormalities.
全外显子测序（WES）可在骨骼异常的产前诊断中提供有诊断意义的结果。但骨骼异常胎儿的表型具有异质性，且我们从正在进行的妊娠中获得的临床信息有限，使得产前诊断变得复杂。因此，以下解释和遗传咨询对临床医生来说仍然是一个挑战。本研究旨在介绍和研究基于三亲的 WES 在五例骨骼异常胎儿中的应用。我们的研究纳入了五例存在胎儿超声骨骼异常的三亲家庭。对胎儿标本和父母外周血进行 WES。通过超声扫描图像呈现胎儿骨骼异常。胎儿 WES 结果显示在五个三亲家庭中，PPIB、CHST3、COL1A1 和 FGFR3 基因存在变异。在两个三亲家庭中发现了遗传变异，而在三个三亲家庭中观察到了新生变异。在 CHST3 中发现了两个新的复合杂合变异（c.437C > A 和 c.1044C > G）。我们呈现了五例存在胎儿骨骼异常的三亲家庭，发现了两个新的变异，并扩大了与骨骼异常相关的变异谱，这有助于在产前建立基因型-表型关系。基于三亲的 WES 可以辅助骨骼异常胎儿的产前诊断和遗传咨询。
