Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1095 Jiefang Avenue, Wuhan, 430030, China.
Orphanet J Rare Dis. 2023 Oct 25;18(1):336. doi: 10.1186/s13023-023-02955-4.
Fetal skeletal dysplasia is a diverse group of degenerative diseases of bone and cartilage disorders that can lead to movement disorder and even death. This study aims to evaluate the diagnostic yield of sonographic examination and genetic testing for fetal skeletal dysplasia.
From September 2015 to April 2021, the study investigated 24 cases with suspected short-limb fetuses, which were obtained from Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology. To identify the causative gene, multiple approaches (including karyotype analysis, copy number variations and whole exome sequencing) were performed on these fetuses. And further segregation analysis of the candidate variant was performed in parents by using Sanger sequencing.
① Out of 24 cases, likely pathogenic variants in FGFR3, FBN2, COL1A2, CUL7 and DYNC2H1 were detected in 6 cases; pathogenic variants in FGFR3, IMPAD1 and GORAB were identified in other 6 cases; and variants in WNT1, FBN1, OBSL1, COL1A1, DYNC2H1 and NEK1, known as Variant of Undetermined Significance, were found in 4 cases. There were no variants detected in the rest 8 cases by the whole exome sequencing. ② Of 24 cases, 12 (50%) were found to carry variants (pathogenic or likely pathogenic) in seven genes with 12 variants. Four fetuses (16.7%) had variants of uncertain significance.
Genetic testing combining with ultrasound scanning enhances the accurate diagnosis of fatal skeletal dysplasia in utero, and then provides appropriate genetic counseling.
胎儿骨骼发育不良是一组多种退行性骨软骨疾病，可导致运动障碍，甚至死亡。本研究旨在评估超声检查和胎儿骨骼发育不良遗传检测的诊断效果。
本研究于 2015 年 9 月至 2021 年 4 月期间，调查了华中科技大学同济医学院附属同济医院的 24 例疑似短肢胎儿。为了鉴定致病基因，对这些胎儿进行了多种方法（包括核型分析、拷贝数变异和全外显子组测序）检测。进一步通过 Sanger 测序在父母中进行候选变异的分离分析。
①在 24 例病例中，6 例检测到 FGFR3、FBN2、COL1A2、CUL7 和 DYNC2H1 中可能致病的变异；6 例中发现 FGFR3、IMPAD1 和 GORAB 的致病性变异；4 例中发现 WNT1、FBN1、OBSL1、COL1A1、DYNC2H1 和 NEK1 的变异，这些变异被认为是意义未明的变异。通过全外显子组测序，其余 8 例未检测到变异。②24 例中，有 12 例（50%）在 7 个基因中携带 12 个变异（致病性或可能致病性）。4 例（16.7%）存在意义未明的变异。
遗传检测与超声扫描相结合，提高了胎儿致死性骨骼发育不良的准确诊断，并提供了适当的遗传咨询。
