Etiological diagnosis of miscarriage by combining use of chromosomal microarray analysis and whole-exome sequencing
Abstract Background Chromosomal microarray analysis (CMA) is being increasingly used to reveal the genetic causes of miscarriage. Nevertheless, approximately half of the time it cannot produce a clear diagnosis. This study aims to investigate the genetic etiology of miscarriage by combining the use...
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BMC
2025-07-01
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| Series: | European Journal of Medical Research |
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| Online Access: | https://doi.org/10.1186/s40001-025-02709-x |
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| author | Jianlong Zhuang Wanyu Fu Ling Gu Xiaofang Ye Junyu Wang Chunnuan Chen |
| author_facet | Jianlong Zhuang Wanyu Fu Ling Gu Xiaofang Ye Junyu Wang Chunnuan Chen |
| author_sort | Jianlong Zhuang |
| collection | DOAJ |
| description | Abstract Background Chromosomal microarray analysis (CMA) is being increasingly used to reveal the genetic causes of miscarriage. Nevertheless, approximately half of the time it cannot produce a clear diagnosis. This study aims to investigate the genetic etiology of miscarriage by combining the use of CMA and whole-exome sequencing (WES). Methods A total of 172 pregnant Chinese women who had suffered miscarriages were enrolled in this study. However, those who had received assisted reproductive services were excluded. Among them, 32 cases without pathogenic copy number variants were further subject to WES analysis, then the relevant variants were confirmed by Sanger sequencing. Results Of the 172 enrolled subjects, CMA was successfully performed in 158 cases, with a detection rate of 91.86%. Among them, 82 cases had chromosomal numerical abnormalities. The most common abnormality was chromosome aneuploidy, followed by triploidy and mosaicism. In addition, nine cases carrying pathogenic copy number variants were also identified. Furthermore, WES detection revealed 11 candidate genes that may have caused miscarriage, including the F5, ANXA5, FGA, NSDHL, ATP8B1, JAK2, CC2D2A, FOXP1, CALCRL, TLE6, and CHRNA1 genes. Conclusions Our findings strengthen that CMA is a rapid and effective genetic etiology diagnosis tool for miscarriages, producing the highest chromosomal abnormality detection rate at a gestational age of 10–11+6 weeks. In addition, several gene variants were identified using WES, which may expand the mutation spectrum for miscarriage and provide more valuable information in understanding the phenotype and genotype correlations. |
| format | Article |
| id | doaj-art-cb9ee507efd347c2884700e5dc9deddd |
| institution | Kabale University |
| issn | 2047-783X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | European Journal of Medical Research |
| spelling | doaj-art-cb9ee507efd347c2884700e5dc9deddd2025-08-20T03:37:29ZengBMCEuropean Journal of Medical Research2047-783X2025-07-013011910.1186/s40001-025-02709-xEtiological diagnosis of miscarriage by combining use of chromosomal microarray analysis and whole-exome sequencingJianlong Zhuang0Wanyu Fu1Ling Gu2Xiaofang Ye3Junyu Wang4Chunnuan Chen5Prenatal Diagnosis Center, Quanzhou Women’s and Children’s HospitalPrenatal Diagnosis Center, Quanzhou Women’s and Children’s HospitalDepartment of Bioinformatics, Berry Genomics CorporationDepartment of Neurology, Rare Disease Medical Center, The Second Affiliated Hospital of Fujian Medical UniversityPrenatal Diagnosis Center, Quanzhou Women’s and Children’s HospitalDepartment of Neurology, Rare Disease Medical Center, The Second Affiliated Hospital of Fujian Medical UniversityAbstract Background Chromosomal microarray analysis (CMA) is being increasingly used to reveal the genetic causes of miscarriage. Nevertheless, approximately half of the time it cannot produce a clear diagnosis. This study aims to investigate the genetic etiology of miscarriage by combining the use of CMA and whole-exome sequencing (WES). Methods A total of 172 pregnant Chinese women who had suffered miscarriages were enrolled in this study. However, those who had received assisted reproductive services were excluded. Among them, 32 cases without pathogenic copy number variants were further subject to WES analysis, then the relevant variants were confirmed by Sanger sequencing. Results Of the 172 enrolled subjects, CMA was successfully performed in 158 cases, with a detection rate of 91.86%. Among them, 82 cases had chromosomal numerical abnormalities. The most common abnormality was chromosome aneuploidy, followed by triploidy and mosaicism. In addition, nine cases carrying pathogenic copy number variants were also identified. Furthermore, WES detection revealed 11 candidate genes that may have caused miscarriage, including the F5, ANXA5, FGA, NSDHL, ATP8B1, JAK2, CC2D2A, FOXP1, CALCRL, TLE6, and CHRNA1 genes. Conclusions Our findings strengthen that CMA is a rapid and effective genetic etiology diagnosis tool for miscarriages, producing the highest chromosomal abnormality detection rate at a gestational age of 10–11+6 weeks. In addition, several gene variants were identified using WES, which may expand the mutation spectrum for miscarriage and provide more valuable information in understanding the phenotype and genotype correlations.https://doi.org/10.1186/s40001-025-02709-xChromosomal microarray analysisWhole-exome sequencingEtiological diagnosisMiscarriageMolecular diagnosis |
| spellingShingle | Jianlong Zhuang Wanyu Fu Ling Gu Xiaofang Ye Junyu Wang Chunnuan Chen Etiological diagnosis of miscarriage by combining use of chromosomal microarray analysis and whole-exome sequencing European Journal of Medical Research Chromosomal microarray analysis Whole-exome sequencing Etiological diagnosis Miscarriage Molecular diagnosis |
| title | Etiological diagnosis of miscarriage by combining use of chromosomal microarray analysis and whole-exome sequencing |
| title_full | Etiological diagnosis of miscarriage by combining use of chromosomal microarray analysis and whole-exome sequencing |
| title_fullStr | Etiological diagnosis of miscarriage by combining use of chromosomal microarray analysis and whole-exome sequencing |
| title_full_unstemmed | Etiological diagnosis of miscarriage by combining use of chromosomal microarray analysis and whole-exome sequencing |
| title_short | Etiological diagnosis of miscarriage by combining use of chromosomal microarray analysis and whole-exome sequencing |
| title_sort | etiological diagnosis of miscarriage by combining use of chromosomal microarray analysis and whole exome sequencing |
| topic | Chromosomal microarray analysis Whole-exome sequencing Etiological diagnosis Miscarriage Molecular diagnosis |
| url | https://doi.org/10.1186/s40001-025-02709-x |
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