Genetic diagnosis of Alport syndrome in 16 Chinese families
Abstract Background Alport syndrome (AS) is a genetically heterogeneous disorder resulting from mutations in the collagen IV genes COL4A3, COL4A4, and COL4A5. The genetic diagnosis of AS is very important to make precise diagnosis and achieve optimal outcomes. Methods In this study, 16 Chinese famil...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2024-03-01
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| Series: | Molecular Genetics & Genomic Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mgg3.2406 |
| _version_ | 1797242598011699200 |
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| author | Tangli Xiao Jun Zhang Li Liu Bo Zhang |
| author_facet | Tangli Xiao Jun Zhang Li Liu Bo Zhang |
| author_sort | Tangli Xiao |
| collection | DOAJ |
| description | Abstract Background Alport syndrome (AS) is a genetically heterogeneous disorder resulting from mutations in the collagen IV genes COL4A3, COL4A4, and COL4A5. The genetic diagnosis of AS is very important to make precise diagnosis and achieve optimal outcomes. Methods In this study, 16 Chinese families with suspected AS were recruited after pedigree analysis, and the clinical presentations were analyzed by a nephrologist. The genetic diagnosis was performed by whole‐exome sequencing (WES) and the disease‐causing variants were confirmed by Sanger sequencing. Results The cohort of probands included seven men and nine women, with a mean age of 19.9 years. Pathological analysis showed slight‐to‐moderate mesangial proliferation, and thin basement membrane was the main findings. Pathogenic variants were revealed by WES in each family, and the co‐segregation with renal presentation was confirmed by PCR. In addition, RT‐PCR analysis showed that the intronic variant led to aberrant splicing. Conclusion Our findings expand the spectrum of AS gene variation, which will inform genetic diagnosis and add to the theoretical basis for the prevention of AS. |
| first_indexed | 2024-04-24T18:41:46Z |
| format | Article |
| id | doaj.art-2c293a15e31946d7b1c395d987158377 |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-04-24T18:41:46Z |
| publishDate | 2024-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-2c293a15e31946d7b1c395d9871583772024-03-27T10:47:28ZengWileyMolecular Genetics & Genomic Medicine2324-92692024-03-01123n/an/a10.1002/mgg3.2406Genetic diagnosis of Alport syndrome in 16 Chinese familiesTangli Xiao0Jun Zhang1Li Liu2Bo Zhang3Department of Nephrology, the Key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Chongqing Clinical Research Center of Kidney and Urology Diseases Xinqiao Hospital, Army Medical University (Third Military Medical University) Chongqing P.R. ChinaDepartment of Nephrology, the Key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Chongqing Clinical Research Center of Kidney and Urology Diseases Xinqiao Hospital, Army Medical University (Third Military Medical University) Chongqing P.R. ChinaDepartment of Nephrology, the Key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Chongqing Clinical Research Center of Kidney and Urology Diseases Xinqiao Hospital, Army Medical University (Third Military Medical University) Chongqing P.R. ChinaDepartment of Nephrology, the Key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Chongqing Clinical Research Center of Kidney and Urology Diseases Xinqiao Hospital, Army Medical University (Third Military Medical University) Chongqing P.R. ChinaAbstract Background Alport syndrome (AS) is a genetically heterogeneous disorder resulting from mutations in the collagen IV genes COL4A3, COL4A4, and COL4A5. The genetic diagnosis of AS is very important to make precise diagnosis and achieve optimal outcomes. Methods In this study, 16 Chinese families with suspected AS were recruited after pedigree analysis, and the clinical presentations were analyzed by a nephrologist. The genetic diagnosis was performed by whole‐exome sequencing (WES) and the disease‐causing variants were confirmed by Sanger sequencing. Results The cohort of probands included seven men and nine women, with a mean age of 19.9 years. Pathological analysis showed slight‐to‐moderate mesangial proliferation, and thin basement membrane was the main findings. Pathogenic variants were revealed by WES in each family, and the co‐segregation with renal presentation was confirmed by PCR. In addition, RT‐PCR analysis showed that the intronic variant led to aberrant splicing. Conclusion Our findings expand the spectrum of AS gene variation, which will inform genetic diagnosis and add to the theoretical basis for the prevention of AS.https://doi.org/10.1002/mgg3.2406Alport syndromeCOL4A3COL4A4COL4A5variants |
| spellingShingle | Tangli Xiao Jun Zhang Li Liu Bo Zhang Genetic diagnosis of Alport syndrome in 16 Chinese families Molecular Genetics & Genomic Medicine Alport syndrome COL4A3 COL4A4 COL4A5 variants |
| title | Genetic diagnosis of Alport syndrome in 16 Chinese families |
| title_full | Genetic diagnosis of Alport syndrome in 16 Chinese families |
| title_fullStr | Genetic diagnosis of Alport syndrome in 16 Chinese families |
| title_full_unstemmed | Genetic diagnosis of Alport syndrome in 16 Chinese families |
| title_short | Genetic diagnosis of Alport syndrome in 16 Chinese families |
| title_sort | genetic diagnosis of alport syndrome in 16 chinese families |
| topic | Alport syndrome COL4A3 COL4A4 COL4A5 variants |
| url | https://doi.org/10.1002/mgg3.2406 |
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