Identification of novel COL4A5 variants and prenatal diagnosis in three large families
Abstract Alport syndrome (AS) is the second-most frequent monogenic kidney disease and 85% of cases are caused by mutations in the genes of the α5 chains of collagen type IV (COL4A5). The early diagnosis and treatment are essential for the prognosis of AS. The clinical phenotypes of AS are very vari...
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Nature Portfolio
2025-03-01
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| Online Access: | https://doi.org/10.1038/s41598-025-92649-7 |
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| author | Baitao Zeng Yao Yu Cong Liu Xinyu Li Qing Lu Zhongfa Chen Jia Chen Jun Zou Bicheng Yang Yanqiu Liu Yongyi Zou |
| author_facet | Baitao Zeng Yao Yu Cong Liu Xinyu Li Qing Lu Zhongfa Chen Jia Chen Jun Zou Bicheng Yang Yanqiu Liu Yongyi Zou |
| author_sort | Baitao Zeng |
| collection | DOAJ |
| description | Abstract Alport syndrome (AS) is the second-most frequent monogenic kidney disease and 85% of cases are caused by mutations in the genes of the α5 chains of collagen type IV (COL4A5). The early diagnosis and treatment are essential for the prognosis of AS. The clinical phenotypes of AS are very variable, which is challenging to diagnose. Genetic diagnosis is sensitive and accurate, which can recognize the affected individuals with mild phenotype for early diagnosis and predict the age at renal failure for early treatment. In addition, genetic testing will offer the available reproductive options, including prenatal diagnosis and preimplantation genetic testing (PGT). In this study, three novel COL4A5 variants (c.1834G > T, c.865G > A and c.1032 + 5G > A) were found. These variants co-segregated with the disease in multiple affected family members. In vitro splicing assay indicated that the c.1032 + 5G > A variant resulted in aberrant splicing involving exon 18 skipping. The healthy babies without these novel COL4A5 variants were born by PGT or prenatal diagnosis, respectively. Three novel variants in COL4A5 gene can provide insights into further genetic counseling or genotype–phenotype correlations. |
| format | Article |
| id | doaj-art-fd31ee4c86a34bc3b1e6e16ae4891847 |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-fd31ee4c86a34bc3b1e6e16ae48918472025-08-20T03:06:00ZengNature PortfolioScientific Reports2045-23222025-03-0115111010.1038/s41598-025-92649-7Identification of novel COL4A5 variants and prenatal diagnosis in three large familiesBaitao Zeng0Yao Yu1Cong Liu2Xinyu Li3Qing Lu4Zhongfa Chen5Jia Chen6Jun Zou7Bicheng Yang8Yanqiu Liu9Yongyi Zou10Department of Medical Genetics, Jiangxi Maternal and Child Health HospitalGongQing Institute of Science and TechnologyReproductive Medicine Cener, Tianjin Central Hospital of Gyngcology ObstetricsNanchang UniversityDepartment of Medical Genetics, Jiangxi Maternal and Child Health HospitalDepartment of Medical Genetics, Jiangxi Maternal and Child Health HospitalReproductive Medicine Center, Jiangxi Maternal and Child Health HospitalDepartment of Medical Genetics, Jiangxi Maternal and Child Health HospitalDepartment of Medical Genetics, Jiangxi Maternal and Child Health HospitalDepartment of Medical Genetics, Jiangxi Maternal and Child Health HospitalDepartment of Medical Genetics, Jiangxi Maternal and Child Health HospitalAbstract Alport syndrome (AS) is the second-most frequent monogenic kidney disease and 85% of cases are caused by mutations in the genes of the α5 chains of collagen type IV (COL4A5). The early diagnosis and treatment are essential for the prognosis of AS. The clinical phenotypes of AS are very variable, which is challenging to diagnose. Genetic diagnosis is sensitive and accurate, which can recognize the affected individuals with mild phenotype for early diagnosis and predict the age at renal failure for early treatment. In addition, genetic testing will offer the available reproductive options, including prenatal diagnosis and preimplantation genetic testing (PGT). In this study, three novel COL4A5 variants (c.1834G > T, c.865G > A and c.1032 + 5G > A) were found. These variants co-segregated with the disease in multiple affected family members. In vitro splicing assay indicated that the c.1032 + 5G > A variant resulted in aberrant splicing involving exon 18 skipping. The healthy babies without these novel COL4A5 variants were born by PGT or prenatal diagnosis, respectively. Three novel variants in COL4A5 gene can provide insights into further genetic counseling or genotype–phenotype correlations.https://doi.org/10.1038/s41598-025-92649-7COL4A5Alport syndromeAberrant splicingPreimplantation genetic testingPrenatal diagnosis |
| spellingShingle | Baitao Zeng Yao Yu Cong Liu Xinyu Li Qing Lu Zhongfa Chen Jia Chen Jun Zou Bicheng Yang Yanqiu Liu Yongyi Zou Identification of novel COL4A5 variants and prenatal diagnosis in three large families Scientific Reports COL4A5 Alport syndrome Aberrant splicing Preimplantation genetic testing Prenatal diagnosis |
| title | Identification of novel COL4A5 variants and prenatal diagnosis in three large families |
| title_full | Identification of novel COL4A5 variants and prenatal diagnosis in three large families |
| title_fullStr | Identification of novel COL4A5 variants and prenatal diagnosis in three large families |
| title_full_unstemmed | Identification of novel COL4A5 variants and prenatal diagnosis in three large families |
| title_short | Identification of novel COL4A5 variants and prenatal diagnosis in three large families |
| title_sort | identification of novel col4a5 variants and prenatal diagnosis in three large families |
| topic | COL4A5 Alport syndrome Aberrant splicing Preimplantation genetic testing Prenatal diagnosis |
| url | https://doi.org/10.1038/s41598-025-92649-7 |
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