Ultrasound and genetic findings in a case series of fetuses presenting vertebral defects
Abstract Purpose This study aimed to summarize the ultrasound and genetic features in a case series of fetuses presenting vertebral defects, to provide useful information for prenatal counseling and prognostic evaluation. Methods Fetuses with vertebral anomalies by a second or third trimester ultras...
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2025-08-01
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| Series: | BMC Pregnancy and Childbirth |
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| Online Access: | https://doi.org/10.1186/s12884-025-07920-6 |
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| author | Wanqin Xie Lin Zhou Ai Hu Jing Chen Jialun Pang Hui Xi Yingchun Luo Jiancheng Hu Shuting Yang Xiaoyang Gao Hanzhe Kuang Wanglan Tang Rui Liu Silong Wang Ying Peng |
| author_facet | Wanqin Xie Lin Zhou Ai Hu Jing Chen Jialun Pang Hui Xi Yingchun Luo Jiancheng Hu Shuting Yang Xiaoyang Gao Hanzhe Kuang Wanglan Tang Rui Liu Silong Wang Ying Peng |
| author_sort | Wanqin Xie |
| collection | DOAJ |
| description | Abstract Purpose This study aimed to summarize the ultrasound and genetic features in a case series of fetuses presenting vertebral defects, to provide useful information for prenatal counseling and prognostic evaluation. Methods Fetuses with vertebral anomalies by a second or third trimester ultrasound screening between January 2020 and April 2024 at a single center were included in the study. Chromosome microarray analysis (CMA) as a first-line diagnostic test was performed. Whole exome sequencing (WES) was further applied to the cases with negative CMA results. Results A total of 12 fetuses presenting vertebral defects were included. Isolated and non-isolated vertebral malformations were reported for eight (66.7%, 8/12) and four (33.3%, 4/12) fetuses, respectively. Congenital heart defects, microphthalmia, and duplicated kidney were among other structural anomalies associated with vertebral malformation in non-isolated cases. Of the 12 fetuses, five (41.7%) had positive results for prenatal diagnosis. CMA detected de novo 16p11.2 deletions (including the TBX6 gene) in three fetuses and a 7q36.1-q36.3 deletion in one fetus, respectively. WES followed by Sanger sequencing validation identified a novel frameshift duplication mutation TBX6 NM_004608.4: c.989_990dup p.(G331Pfs*168) in trans with the hypomorphic T-C-A haplotype (defined by SNPs rs2289292, rs3809624, and rs3809627) on the opposite allele in a fetus with a negative result for pathogenic copy number variants. There was no statistically significant difference in diagnostic yield between the isolated (25.0%, 2/8) and non-isolated (75%, 3/4) cases (Fisher exact test, P = 0.141). In all cases, six (50%, 6/12) had termination of pregnancy, three (25%, 3/12) had live birth with normal development at the latest follow-up, and three declined or were lost to follow-up. All live births were from cases with negative CMA and WES results. Conclusion CMA has a good performance for the diagnosis of fetuses presenting vertebral defects, and WES can further improve the diagnostic yield from the cases with negative CMA results. More studies are needed to reveal the etiologies and enhance the prenatal management of fetal vertebral defects. |
| format | Article |
| id | doaj-art-e2592c8d3dea429ca8d859838188c3e3 |
| institution | Kabale University |
| issn | 1471-2393 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
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| series | BMC Pregnancy and Childbirth |
| spelling | doaj-art-e2592c8d3dea429ca8d859838188c3e32025-08-20T03:46:28ZengBMCBMC Pregnancy and Childbirth1471-23932025-08-012511810.1186/s12884-025-07920-6Ultrasound and genetic findings in a case series of fetuses presenting vertebral defectsWanqin Xie0Lin Zhou1Ai Hu2Jing Chen3Jialun Pang4Hui Xi5Yingchun Luo6Jiancheng Hu7Shuting Yang8Xiaoyang Gao9Hanzhe Kuang10Wanglan Tang11Rui Liu12Silong Wang13Ying Peng14Department of Medical Genetics, National Health Commission Key Laboratory of Birth Defects for Research and Prevention, Hunan Provincial Maternal and Child Health Care HospitalDepartment of Medical Genetics, National Health Commission Key Laboratory of Birth Defects for Research and Prevention, Hunan Provincial Maternal and Child Health Care HospitalDepartment of Medical Genetics, National Health Commission Key Laboratory of Birth Defects for Research and Prevention, Hunan Provincial Maternal and Child Health Care HospitalDepartment of Medical Genetics, National Health Commission Key Laboratory of Birth Defects for Research and Prevention, Hunan Provincial Maternal and Child Health Care HospitalDepartment of Medical Genetics, National Health Commission Key Laboratory of Birth Defects for Research and Prevention, Hunan Provincial Maternal and Child Health Care HospitalDepartment of Medical Genetics, National Health Commission Key Laboratory of Birth Defects for Research and Prevention, Hunan Provincial Maternal and Child Health Care HospitalDepartment of Medical Genetics, National Health Commission Key Laboratory of Birth Defects for Research and Prevention, Hunan Provincial Maternal and Child Health Care HospitalDepartment of Medical Genetics, National Health Commission Key Laboratory of Birth Defects for Research and Prevention, Hunan Provincial Maternal and Child Health Care HospitalDepartment of Medical Genetics, National Health Commission Key Laboratory of Birth Defects for Research and Prevention, Hunan Provincial Maternal and Child Health Care HospitalDepartment of Medical Genetics, National Health Commission Key Laboratory of Birth Defects for Research and Prevention, Hunan Provincial Maternal and Child Health Care HospitalDepartment of Medical Genetics, National Health Commission Key Laboratory of Birth Defects for Research and Prevention, Hunan Provincial Maternal and Child Health Care HospitalDepartment of Medical Genetics, National Health Commission Key Laboratory of Birth Defects for Research and Prevention, Hunan Provincial Maternal and Child Health Care HospitalDepartment of Medical Genetics, National Health Commission Key Laboratory of Birth Defects for Research and Prevention, Hunan Provincial Maternal and Child Health Care HospitalDepartment of Medical Genetics, National Health Commission Key Laboratory of Birth Defects for Research and Prevention, Hunan Provincial Maternal and Child Health Care HospitalDepartment of Medical Genetics, National Health Commission Key Laboratory of Birth Defects for Research and Prevention, Hunan Provincial Maternal and Child Health Care HospitalAbstract Purpose This study aimed to summarize the ultrasound and genetic features in a case series of fetuses presenting vertebral defects, to provide useful information for prenatal counseling and prognostic evaluation. Methods Fetuses with vertebral anomalies by a second or third trimester ultrasound screening between January 2020 and April 2024 at a single center were included in the study. Chromosome microarray analysis (CMA) as a first-line diagnostic test was performed. Whole exome sequencing (WES) was further applied to the cases with negative CMA results. Results A total of 12 fetuses presenting vertebral defects were included. Isolated and non-isolated vertebral malformations were reported for eight (66.7%, 8/12) and four (33.3%, 4/12) fetuses, respectively. Congenital heart defects, microphthalmia, and duplicated kidney were among other structural anomalies associated with vertebral malformation in non-isolated cases. Of the 12 fetuses, five (41.7%) had positive results for prenatal diagnosis. CMA detected de novo 16p11.2 deletions (including the TBX6 gene) in three fetuses and a 7q36.1-q36.3 deletion in one fetus, respectively. WES followed by Sanger sequencing validation identified a novel frameshift duplication mutation TBX6 NM_004608.4: c.989_990dup p.(G331Pfs*168) in trans with the hypomorphic T-C-A haplotype (defined by SNPs rs2289292, rs3809624, and rs3809627) on the opposite allele in a fetus with a negative result for pathogenic copy number variants. There was no statistically significant difference in diagnostic yield between the isolated (25.0%, 2/8) and non-isolated (75%, 3/4) cases (Fisher exact test, P = 0.141). In all cases, six (50%, 6/12) had termination of pregnancy, three (25%, 3/12) had live birth with normal development at the latest follow-up, and three declined or were lost to follow-up. All live births were from cases with negative CMA and WES results. Conclusion CMA has a good performance for the diagnosis of fetuses presenting vertebral defects, and WES can further improve the diagnostic yield from the cases with negative CMA results. More studies are needed to reveal the etiologies and enhance the prenatal management of fetal vertebral defects.https://doi.org/10.1186/s12884-025-07920-6Congenital scoliosis16p11.2 deletionTBX6Chromosome microarray analysisExome sequencing |
| spellingShingle | Wanqin Xie Lin Zhou Ai Hu Jing Chen Jialun Pang Hui Xi Yingchun Luo Jiancheng Hu Shuting Yang Xiaoyang Gao Hanzhe Kuang Wanglan Tang Rui Liu Silong Wang Ying Peng Ultrasound and genetic findings in a case series of fetuses presenting vertebral defects BMC Pregnancy and Childbirth Congenital scoliosis 16p11.2 deletion TBX6 Chromosome microarray analysis Exome sequencing |
| title | Ultrasound and genetic findings in a case series of fetuses presenting vertebral defects |
| title_full | Ultrasound and genetic findings in a case series of fetuses presenting vertebral defects |
| title_fullStr | Ultrasound and genetic findings in a case series of fetuses presenting vertebral defects |
| title_full_unstemmed | Ultrasound and genetic findings in a case series of fetuses presenting vertebral defects |
| title_short | Ultrasound and genetic findings in a case series of fetuses presenting vertebral defects |
| title_sort | ultrasound and genetic findings in a case series of fetuses presenting vertebral defects |
| topic | Congenital scoliosis 16p11.2 deletion TBX6 Chromosome microarray analysis Exome sequencing |
| url | https://doi.org/10.1186/s12884-025-07920-6 |
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