Medical Genetics Center, Jiangmen Maternity and Child Health Care Hospital, Jiangmen, Guangdong 529000, China; Department of Medical Imaging Center, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, Guangdong 510080, China.
Medical Genetics Center, Jiangmen Maternity and Child Health Care Hospital, Jiangmen, Guangdong 529000, China; Halo Genetics, Guangzhou, Guangdong 510000, China.
Clin Chim Acta. 2020 Aug;507:187-193. doi: 10.1016/j.cca.2020.04.031. Epub 2020 Apr 28.
Skeletal dysplasias account for nearly 10% of fetal structural malformations detected by ultrasonography. This clinically heterogeneous group of genetic anomaly includes at least 461 genetic skeletal disorders with extreme clinical, phenotypic, and genetic heterogeneities, thus, significantly complicates accurate diagnosis. Researches have used whole exome sequencing (WES) for prenatal molecular diagnoses of skeletal dysplasias, however, data are still limited.
DNA extracted from umbilical cord blood or amniocytes from fetuses suspected of skeletal dysplasias based on ultrasound evaluations were analyzed by WES. Blood samples were taken from the parents of the positive fetuses for co-segregation analysis using Sanger sequencing.
Definitive molecular diagnosis was made in 6/8 (75%) cases, comprised of 5 de novo disease-causing changes in 3 genes (FGFR3, COL2A1, and COL1A2) and one proband with a biallelic deficiency for Lamin B Receptor(LBR),and including 3 novel variants. All fetuses had no detectable copy number variation (CNV) from sequencing results.
Our study suggests that WES is an efficient approach for prenatal diagnosis of fetuses suspected of skeletal abnormalities and contributes to parental genetics counseling and pregnancy management.
骨骼发育不良占超声检测到的胎儿结构畸形的近 10%。这组临床异质性的遗传异常包括至少 461 种遗传骨骼疾病，具有极端的临床、表型和遗传异质性，因此显著增加了准确诊断的难度。研究人员已经使用全外显子组测序（WES）对骨骼发育不良进行产前分子诊断，然而，数据仍然有限。
对基于超声评估怀疑患有骨骼发育不良的胎儿的脐带血或羊水细胞中的 DNA 进行 WES 分析。对阳性胎儿的父母进行 Sanger 测序进行共分离分析，以获取血液样本。
在 8 例（75%）中做出了明确的分子诊断，包括 3 个基因（FGFR3、COL2A1 和 COL1A2）中的 5 个新生致病变异和 1 个 Lamin B Receptor（LBR）双等位基因缺陷的先证者，包括 3 个新的变异。所有胎儿的测序结果均未检测到拷贝数变异（CNV）。
我们的研究表明，WES 是一种有效的产前诊断胎儿骨骼异常的方法，有助于父母的遗传咨询和妊娠管理。
