Prenatal Cases Reflect the Complexity of the <i>COL1A1/2</i> Associated Osteogenesis Imperfecta
Introduction: Osteogenesis imperfecta (OI) is a rare mendelian skeletal dysplasia with autosomal dominant or recessive inheritance pattern, and almost the most common primary osteoporosis in prenatal settings. The diversity of clinical presentation and genetic etiology in prenatal OI cases presents...
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MDPI AG
2022-09-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/13/9/1578 |
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| author | Kai Yang Yan Liu Jue Wu Jing Zhang Hua-ying Hu You-sheng Yan Wen-qi Chen Shu-fa Yang Li-juan Sun Yong-qing Sun Qing-qing Wu Cheng-hong Yin |
| author_facet | Kai Yang Yan Liu Jue Wu Jing Zhang Hua-ying Hu You-sheng Yan Wen-qi Chen Shu-fa Yang Li-juan Sun Yong-qing Sun Qing-qing Wu Cheng-hong Yin |
| author_sort | Kai Yang |
| collection | DOAJ |
| description | Introduction: Osteogenesis imperfecta (OI) is a rare mendelian skeletal dysplasia with autosomal dominant or recessive inheritance pattern, and almost the most common primary osteoporosis in prenatal settings. The diversity of clinical presentation and genetic etiology in prenatal OI cases presents a challenge to counseling yet has seldom been discussed in previous studies. Methods: Ten cases with suspected fetal OI were enrolled and submitted to a genetic detection using conventional karyotyping, chromosomal microarray analysis (CMA), and whole-exome sequencing (WES). Sanger sequencing was used as the validation method for potential diagnostic variants. In silico analysis of specific missense variants was also performed. Results: The karyotyping and CMA results of these cases were normal, while WES identified OI-associated variants in the <i>COL1A1/2</i> genes in all ten cases. Six of these variants were novel. Additionally, four cases here exhibited distinctive clinical and/or genetic characteristics, including the situations of intrafamilial phenotypic variability, parental mosaicism, and “dual nosogenesis” (mutations in collagen I and another gene). Conclusion: Our study not only expands the spectrum of <i>COL1A1/2</i>-related OI, but also highlights the complexity that occurs in prenatal OI and the importance of clarifying its pathogenic mechanisms. |
| first_indexed | 2024-03-09T23:56:37Z |
| format | Article |
| id | doaj.art-95397cecf32c4b52803c18c533b8825d |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-09T23:56:37Z |
| publishDate | 2022-09-01 |
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| record_format | Article |
| series | Genes |
| spelling | doaj.art-95397cecf32c4b52803c18c533b8825d2023-11-23T16:24:28ZengMDPI AGGenes2073-44252022-09-01139157810.3390/genes13091578Prenatal Cases Reflect the Complexity of the <i>COL1A1/2</i> Associated Osteogenesis ImperfectaKai Yang0Yan Liu1Jue Wu2Jing Zhang3Hua-ying Hu4You-sheng Yan5Wen-qi Chen6Shu-fa Yang7Li-juan Sun8Yong-qing Sun9Qing-qing Wu10Cheng-hong Yin11Prenatal Diagnosis Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, ChinaPrenatal Diagnosis Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, ChinaTranslational Medicine Research Center, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing 100039, ChinaPrenatal Diagnosis Center, Shijiazhuang Obstetrics and Gynecology Hospital, Shijiazhuang 050011, ChinaJiaen Genetics Laboratory, Beijing Jiaen Hospital, Beijing 100083, ChinaPrenatal Diagnosis Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, ChinaPrenatal Diagnosis Center, Shijiazhuang Obstetrics and Gynecology Hospital, Shijiazhuang 050011, ChinaPrenatal Diagnosis Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, ChinaDepartment of Ultrasound, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, ChinaPrenatal Diagnosis Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, ChinaDepartment of Ultrasound, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, ChinaPrenatal Diagnosis Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, ChinaIntroduction: Osteogenesis imperfecta (OI) is a rare mendelian skeletal dysplasia with autosomal dominant or recessive inheritance pattern, and almost the most common primary osteoporosis in prenatal settings. The diversity of clinical presentation and genetic etiology in prenatal OI cases presents a challenge to counseling yet has seldom been discussed in previous studies. Methods: Ten cases with suspected fetal OI were enrolled and submitted to a genetic detection using conventional karyotyping, chromosomal microarray analysis (CMA), and whole-exome sequencing (WES). Sanger sequencing was used as the validation method for potential diagnostic variants. In silico analysis of specific missense variants was also performed. Results: The karyotyping and CMA results of these cases were normal, while WES identified OI-associated variants in the <i>COL1A1/2</i> genes in all ten cases. Six of these variants were novel. Additionally, four cases here exhibited distinctive clinical and/or genetic characteristics, including the situations of intrafamilial phenotypic variability, parental mosaicism, and “dual nosogenesis” (mutations in collagen I and another gene). Conclusion: Our study not only expands the spectrum of <i>COL1A1/2</i>-related OI, but also highlights the complexity that occurs in prenatal OI and the importance of clarifying its pathogenic mechanisms.https://www.mdpi.com/2073-4425/13/9/1578Osteogenesis imperfecta<i>COL1A1</i><i>COL1A2</i><i>CANT1</i><i>RMRP</i> |
| spellingShingle | Kai Yang Yan Liu Jue Wu Jing Zhang Hua-ying Hu You-sheng Yan Wen-qi Chen Shu-fa Yang Li-juan Sun Yong-qing Sun Qing-qing Wu Cheng-hong Yin Prenatal Cases Reflect the Complexity of the <i>COL1A1/2</i> Associated Osteogenesis Imperfecta Genes Osteogenesis imperfecta <i>COL1A1</i> <i>COL1A2</i> <i>CANT1</i> <i>RMRP</i> |
| title | Prenatal Cases Reflect the Complexity of the <i>COL1A1/2</i> Associated Osteogenesis Imperfecta |
| title_full | Prenatal Cases Reflect the Complexity of the <i>COL1A1/2</i> Associated Osteogenesis Imperfecta |
| title_fullStr | Prenatal Cases Reflect the Complexity of the <i>COL1A1/2</i> Associated Osteogenesis Imperfecta |
| title_full_unstemmed | Prenatal Cases Reflect the Complexity of the <i>COL1A1/2</i> Associated Osteogenesis Imperfecta |
| title_short | Prenatal Cases Reflect the Complexity of the <i>COL1A1/2</i> Associated Osteogenesis Imperfecta |
| title_sort | prenatal cases reflect the complexity of the i col1a1 2 i associated osteogenesis imperfecta |
| topic | Osteogenesis imperfecta <i>COL1A1</i> <i>COL1A2</i> <i>CANT1</i> <i>RMRP</i> |
| url | https://www.mdpi.com/2073-4425/13/9/1578 |
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