Incomplete Trisomy Rescue Reveals the Mechanism Underlying Discordance Between Noninvasive Prenatal Screening and Prenatal Diagnosis
ABSTRACT Background Uniparental disomy (UPD) is a specific type of chromosomal variation in which both chromosomes of a homologous pair are inherited from the same parent. It is responsible for a wide range of disorders. Monosomy rescue and trisomy rescue are the two main hypotheses of UPD generatio...
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Wiley
2025-03-01
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| Series: | Molecular Genetics & Genomic Medicine |
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| Online Access: | https://doi.org/10.1002/mgg3.70091 |
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| author | Yanan Wang Yong Zhou Yuqiong Chai Weiwei Zang Hongchao Wang Fan Yin Qianqian Tan Zhigang Chen |
| author_facet | Yanan Wang Yong Zhou Yuqiong Chai Weiwei Zang Hongchao Wang Fan Yin Qianqian Tan Zhigang Chen |
| author_sort | Yanan Wang |
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| description | ABSTRACT Background Uniparental disomy (UPD) is a specific type of chromosomal variation in which both chromosomes of a homologous pair are inherited from the same parent. It is responsible for a wide range of disorders. Monosomy rescue and trisomy rescue are the two main hypotheses of UPD generation. Methods An older parturient woman with a positive noninvasive prenatal screening (NIPS) test but a negative prenatal diagnosis was referred to the hospital. Trio whole exome sequencing (trio‐WES) and ddPCR were further performed. Results Utilizing Trio‐WES analysis, our research identified a maternal segmental UPD on chromosome 16, characterized by isodisomic genomic segments at the ends of the chromosome arms and heterodisomic genomic segments near the centromere. Moreover, several nuanced signs pointing to the paternal chromosome 16 were discovered, suggesting a low level of trisomy 16 mosaicism. A homozygous missense mutation (c.1499C>T; p.Ala500Val) was also detected in the fetal TBC1D24 gene, passed down from the heterozygous carrier mother. Furthermore, ddPCR analysis verified a 3% mosaic level of trisomy 16. Conclusion We have quantitatively verified for the first time a combination of trisomy 16 mosaicism and maternal segmental UPD 16 due to incomplete trisomy rescue, illuminating the cause of the mismatch between positive NIPS and negative prenatal diagnoses. |
| format | Article |
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| language | English |
| publishDate | 2025-03-01 |
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| spelling | doaj-art-c7edcc755d3548379fbdea05bdd7271e2025-08-20T01:49:47ZengWileyMolecular Genetics & Genomic Medicine2324-92692025-03-01133n/an/a10.1002/mgg3.70091Incomplete Trisomy Rescue Reveals the Mechanism Underlying Discordance Between Noninvasive Prenatal Screening and Prenatal DiagnosisYanan Wang0Yong Zhou1Yuqiong Chai2Weiwei Zang3Hongchao Wang4Fan Yin5Qianqian Tan6Zhigang Chen7Department of Genetics and Prenatal Diagnosis Luoyang Maternal and Child Health Hospital Luoyang People's Republic of ChinaPuluo (Wuhan) Medical Biotechnology Co. Ltd Wuhan People's Republic of ChinaDepartment of Genetics and Prenatal Diagnosis Luoyang Maternal and Child Health Hospital Luoyang People's Republic of ChinaDepartment of Genetics and Prenatal Diagnosis Luoyang Maternal and Child Health Hospital Luoyang People's Republic of ChinaImaging Department of Luoyang Maternal and Child Health Hospital Luoyang Henan Province ChinaPuluo (Wuhan) Medical Biotechnology Co. Ltd Wuhan People's Republic of ChinaPuluo (Wuhan) Medical Biotechnology Co. Ltd Wuhan People's Republic of ChinaPuluo (Wuhan) Medical Biotechnology Co. Ltd Wuhan People's Republic of ChinaABSTRACT Background Uniparental disomy (UPD) is a specific type of chromosomal variation in which both chromosomes of a homologous pair are inherited from the same parent. It is responsible for a wide range of disorders. Monosomy rescue and trisomy rescue are the two main hypotheses of UPD generation. Methods An older parturient woman with a positive noninvasive prenatal screening (NIPS) test but a negative prenatal diagnosis was referred to the hospital. Trio whole exome sequencing (trio‐WES) and ddPCR were further performed. Results Utilizing Trio‐WES analysis, our research identified a maternal segmental UPD on chromosome 16, characterized by isodisomic genomic segments at the ends of the chromosome arms and heterodisomic genomic segments near the centromere. Moreover, several nuanced signs pointing to the paternal chromosome 16 were discovered, suggesting a low level of trisomy 16 mosaicism. A homozygous missense mutation (c.1499C>T; p.Ala500Val) was also detected in the fetal TBC1D24 gene, passed down from the heterozygous carrier mother. Furthermore, ddPCR analysis verified a 3% mosaic level of trisomy 16. Conclusion We have quantitatively verified for the first time a combination of trisomy 16 mosaicism and maternal segmental UPD 16 due to incomplete trisomy rescue, illuminating the cause of the mismatch between positive NIPS and negative prenatal diagnoses.https://doi.org/10.1002/mgg3.70091incomplete trisomy rescuenoninvasive prenatal screeningTBC1D24trio‐WESuniparental disomy |
| spellingShingle | Yanan Wang Yong Zhou Yuqiong Chai Weiwei Zang Hongchao Wang Fan Yin Qianqian Tan Zhigang Chen Incomplete Trisomy Rescue Reveals the Mechanism Underlying Discordance Between Noninvasive Prenatal Screening and Prenatal Diagnosis Molecular Genetics & Genomic Medicine incomplete trisomy rescue noninvasive prenatal screening TBC1D24 trio‐WES uniparental disomy |
| title | Incomplete Trisomy Rescue Reveals the Mechanism Underlying Discordance Between Noninvasive Prenatal Screening and Prenatal Diagnosis |
| title_full | Incomplete Trisomy Rescue Reveals the Mechanism Underlying Discordance Between Noninvasive Prenatal Screening and Prenatal Diagnosis |
| title_fullStr | Incomplete Trisomy Rescue Reveals the Mechanism Underlying Discordance Between Noninvasive Prenatal Screening and Prenatal Diagnosis |
| title_full_unstemmed | Incomplete Trisomy Rescue Reveals the Mechanism Underlying Discordance Between Noninvasive Prenatal Screening and Prenatal Diagnosis |
| title_short | Incomplete Trisomy Rescue Reveals the Mechanism Underlying Discordance Between Noninvasive Prenatal Screening and Prenatal Diagnosis |
| title_sort | incomplete trisomy rescue reveals the mechanism underlying discordance between noninvasive prenatal screening and prenatal diagnosis |
| topic | incomplete trisomy rescue noninvasive prenatal screening TBC1D24 trio‐WES uniparental disomy |
| url | https://doi.org/10.1002/mgg3.70091 |
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