Pan Pingshan, Huang Dongbing, Wei Jiangxuan, He Wei, Huang Peng, Yi Sheng, Huang Jing, Meng Dahua, Tan Shuyin, Li Xinyan, Wei Hongwei, Wang Linlin
Prenatal Diagnosis Center, The Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, People's Republic of China.
Mol Genet Genomic Med. 2025 Feb;13(2):e70076. doi: 10.1002/mgg3.70076.
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.
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.
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.
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.
本研究旨在探讨染色体微阵列分析（CMA）和全外显子组测序（WES）在诊断为马蹄内翻足（TE）胎儿中的应用，并探索导致TE的遗传因素。
该研究回顾了2015年1月至2023年12月期间共241例TE胎儿，根据是否存在其他超声异常将其分为两组：孤立性TE组163例（67.6%）和综合征性TE组78例（32.4%）。对所有病例进行了核型分析和CMA，对核型和CMA结果正常的18例病例进行了WES。
结果表明，核型分析和CMA的总检出率为16.2%（39/241）。此外，孤立性TE组和综合征性TE组的核型分析和CMA检出率分别为10.4%（17/163）和28.2%（22/78），差异有统计学意义（p<0.05）。对18例核型分析和CMA结果正常的胎儿进行了WES。共鉴定出6例，包括5例致病性单核苷酸变异（SNV）和1例意义未明变异（VUS），检出率为33.3%（6/18）。鉴定出的SNV与RIT1、GNPNAT1、PEX1、RYR1、ASCC1和GDAP1基因相关。孤立性TE组和综合征性TE组的WES检出率分别为25%（1/4）和35.7%（5/14），差异无统计学意义（p>0.05）。TE胎儿的基因检测总体诊断率为18.7%（45/241）。
当产前超声识别出胎儿TE时，染色体核型分析和CMA应被视为一线诊断试验。与以往研究不同，本研究建议在孤立性和综合征性胎儿TE的CMA结果正常的情况下进行WES。
