The Genetics of 241 Fetuses With Talipes Equinovarus: A 8‐Year Monocentric Retrospective Study

ABSTRACT Objective This study aims to investigate the utility of chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in fetuses diagnosed with talipes equinovarus (TE), as well as to explore the genetic factors contributing to TE. Methods The study reviewed a total of 241 fetuses...

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Main Authors: Pingshan Pan, Dongbing Huang, Jiangxuan Wei, Wei He, Peng Huang, Sheng Yi, Jing Huang, Dahua Meng, Shuyin Tan, Xinyan Li, Hongwei Wei, Linlin Wang
Format: Article
Language:English
Published: Wiley 2025-02-01
Series:Molecular Genetics & Genomic Medicine
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Online Access:https://doi.org/10.1002/mgg3.70076
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author Pingshan Pan
Dongbing Huang
Jiangxuan Wei
Wei He
Peng Huang
Sheng Yi
Jing Huang
Dahua Meng
Shuyin Tan
Xinyan Li
Hongwei Wei
Linlin Wang
author_facet Pingshan Pan
Dongbing Huang
Jiangxuan Wei
Wei He
Peng Huang
Sheng Yi
Jing Huang
Dahua Meng
Shuyin Tan
Xinyan Li
Hongwei Wei
Linlin Wang
author_sort Pingshan Pan
collection DOAJ
description ABSTRACT Objective This study aims to investigate the utility of chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in fetuses diagnosed with talipes equinovarus (TE), as well as to explore the genetic factors contributing to TE. Methods The study reviewed a total of 241 fetuses with TE between January 2015 and December 2023, categorizing them into two groups based on the absence or presence of additional ultrasound anomalies: 163 cases (67.6%) in the isolated TE group and 78 cases (32.4%) in the syndromic TE group. Karyotyping and CMA were performed for all cases, with WES being performed for 18 cases that had normal karyotype and CMA results. Results The results indicated a total detection rate of 16.2% (39/241) using karyotyping and CMA. Furthermore, the detection rates of karyotyping and CMA in the isolated TE group and syndromic TE group were 10.4% (17/163) and 28.2% (22/78) respectively, showing a statistically significant difference (p < 0.05). WES was conducted on 18 fetuses with normal karyotyping and CMA results. A total of six cases, consisting of five cases with pathogenic single nucleotide variant (SNV) and one case of variants of uncertain significance (VUS), were identified, resulting in a detection rate of 33.3% (6/18). The identified SNVs was associated with the RIT1, GNPNAT1, PEX1, RYR1, ASCC1, and GDAP1 genes. The detection rates of WES in the isolated TE group and syndromic TE group were 25% (1/4) and 35.7% (5/14) respectively, with no statistically significant difference (p > 0.05). The overall diagnostic yield of genetic testing was 18.7% (45/241) in fetuses with TE. Conclusion When prenatal ultrasound identifies fetal TE, chromosome karyotyping and CMA should be considered as the first‐line diagnostic tests. Unlike previous studies, this study recommended WES in cases of normal CMA results for both isolated and syndromic fetal TE.
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spelling doaj-art-66a8aee4283b4d0884f847ffa3bb250b2025-08-20T02:15:33ZengWileyMolecular Genetics & Genomic Medicine2324-92692025-02-01132n/an/a10.1002/mgg3.70076The Genetics of 241 Fetuses With Talipes Equinovarus: A 8‐Year Monocentric Retrospective StudyPingshan Pan0Dongbing Huang1Jiangxuan Wei2Wei He3Peng Huang4Sheng Yi5Jing Huang6Dahua Meng7Shuyin Tan8Xinyan Li9Hongwei Wei10Linlin Wang11Prenatal Diagnosis Center The Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region Nanning People's Republic of ChinaPrenatal Diagnosis Center The Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region Nanning People's Republic of ChinaPrenatal Diagnosis Center The Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region Nanning People's Republic of ChinaPrenatal Diagnosis Center The Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region Nanning People's Republic of ChinaPrenatal Diagnosis Center The Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region Nanning People's Republic of ChinaPrenatal Diagnosis Center The Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region Nanning People's Republic of ChinaPrenatal Diagnosis Center The Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region Nanning People's Republic of ChinaPrenatal Diagnosis Center The Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region Nanning People's Republic of ChinaPrenatal Diagnosis Center The Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region Nanning People's Republic of ChinaPrenatal Diagnosis Center The Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region Nanning People's Republic of ChinaPrenatal Diagnosis Center The Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region Nanning People's Republic of ChinaPrenatal Diagnosis Center The Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region Nanning People's Republic of ChinaABSTRACT Objective This study aims to investigate the utility of chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in fetuses diagnosed with talipes equinovarus (TE), as well as to explore the genetic factors contributing to TE. Methods The study reviewed a total of 241 fetuses with TE between January 2015 and December 2023, categorizing them into two groups based on the absence or presence of additional ultrasound anomalies: 163 cases (67.6%) in the isolated TE group and 78 cases (32.4%) in the syndromic TE group. Karyotyping and CMA were performed for all cases, with WES being performed for 18 cases that had normal karyotype and CMA results. Results The results indicated a total detection rate of 16.2% (39/241) using karyotyping and CMA. Furthermore, the detection rates of karyotyping and CMA in the isolated TE group and syndromic TE group were 10.4% (17/163) and 28.2% (22/78) respectively, showing a statistically significant difference (p < 0.05). WES was conducted on 18 fetuses with normal karyotyping and CMA results. A total of six cases, consisting of five cases with pathogenic single nucleotide variant (SNV) and one case of variants of uncertain significance (VUS), were identified, resulting in a detection rate of 33.3% (6/18). The identified SNVs was associated with the RIT1, GNPNAT1, PEX1, RYR1, ASCC1, and GDAP1 genes. The detection rates of WES in the isolated TE group and syndromic TE group were 25% (1/4) and 35.7% (5/14) respectively, with no statistically significant difference (p > 0.05). The overall diagnostic yield of genetic testing was 18.7% (45/241) in fetuses with TE. Conclusion When prenatal ultrasound identifies fetal TE, chromosome karyotyping and CMA should be considered as the first‐line diagnostic tests. Unlike previous studies, this study recommended WES in cases of normal CMA results for both isolated and syndromic fetal TE.https://doi.org/10.1002/mgg3.70076chromosome microarray analysisprenatal diagnosistalipes equinovaruswhole exome sequencing
spellingShingle Pingshan Pan
Dongbing Huang
Jiangxuan Wei
Wei He
Peng Huang
Sheng Yi
Jing Huang
Dahua Meng
Shuyin Tan
Xinyan Li
Hongwei Wei
Linlin Wang
The Genetics of 241 Fetuses With Talipes Equinovarus: A 8‐Year Monocentric Retrospective Study
Molecular Genetics & Genomic Medicine
chromosome microarray analysis
prenatal diagnosis
talipes equinovarus
whole exome sequencing
title The Genetics of 241 Fetuses With Talipes Equinovarus: A 8‐Year Monocentric Retrospective Study
title_full The Genetics of 241 Fetuses With Talipes Equinovarus: A 8‐Year Monocentric Retrospective Study
title_fullStr The Genetics of 241 Fetuses With Talipes Equinovarus: A 8‐Year Monocentric Retrospective Study
title_full_unstemmed The Genetics of 241 Fetuses With Talipes Equinovarus: A 8‐Year Monocentric Retrospective Study
title_short The Genetics of 241 Fetuses With Talipes Equinovarus: A 8‐Year Monocentric Retrospective Study
title_sort genetics of 241 fetuses with talipes equinovarus a 8 year monocentric retrospective study
topic chromosome microarray analysis
prenatal diagnosis
talipes equinovarus
whole exome sequencing
url https://doi.org/10.1002/mgg3.70076
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