Three exonic variants in the COL4A5 gene alter RNA splicing in a minigene assay
Abstract Background X‐linked Alport syndrome (XLAS) is an inherited renal disease caused by rare variants of COL4A5 on chromosome Xq22. Many studies have indicated that single nucleotide variants (SNVs) in exons can disrupt normal splicing process of the pre‐mRNA by altering various splicing regulat...
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| Format: | Article |
| Language: | English |
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Wiley
2024-02-01
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| Series: | Molecular Genetics & Genomic Medicine |
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| Online Access: | https://doi.org/10.1002/mgg3.2395 |
| _version_ | 1797294639814803456 |
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| author | Ran Zhang Yanhua Lang Xiaomeng Shi Yiyin Zhang Xuyan Liu Fengjiao Pan Dan Qiao Xin Teng Leping Shao |
| author_facet | Ran Zhang Yanhua Lang Xiaomeng Shi Yiyin Zhang Xuyan Liu Fengjiao Pan Dan Qiao Xin Teng Leping Shao |
| author_sort | Ran Zhang |
| collection | DOAJ |
| description | Abstract Background X‐linked Alport syndrome (XLAS) is an inherited renal disease caused by rare variants of COL4A5 on chromosome Xq22. Many studies have indicated that single nucleotide variants (SNVs) in exons can disrupt normal splicing process of the pre‐mRNA by altering various splicing regulatory signals. The male patients with XLAS have a strong genotype–phenotype correlation. Confirming the effect of variants on splicing can help to predict kidney prognosis. This study aimed to investigate whether single nucleotide substitutions, located within three bases at the 5′ end of the exons or internal position of the exons in COL4A5 gene, cause aberrant splicing process. Methods We analyzed 401 SNVs previously presumed missense and nonsense variants in COL4A5 gene by bioinformatics programs and identified candidate variants that may affect the splicing of pre‐mRNA via minigene assays. Results Our study indicated three of eight candidate variants induced complete or partial exon skipping. Variants c.2678G>C and c.2918G>A probably disturb classic splice sites leading to corresponding exon skipping. Variant c.3700C>T may disrupt splicing enhancer motifs accompanying with generation of splicing silencer sequences resulting in the skipping of exon 41. Conclusion Our study revealed that two missense variants positioned the first nucleotides of the 5′ end of COL4A5 exons and one internal exonic nonsense variant caused aberrant splicing. Importantly, this study emphasized the necessity of assessing the effects of SNVs at the mRNA level. |
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| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-03-07T21:33:13Z |
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| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-e5e85b9bb18747efb15524a019e0b6212024-02-26T14:52:29ZengWileyMolecular Genetics & Genomic Medicine2324-92692024-02-01122n/an/a10.1002/mgg3.2395Three exonic variants in the COL4A5 gene alter RNA splicing in a minigene assayRan Zhang0Yanhua Lang1Xiaomeng Shi2Yiyin Zhang3Xuyan Liu4Fengjiao Pan5Dan Qiao6Xin Teng7Leping Shao8Department of Nephrology the Affiliated Qingdao Municipal Hospital of Qingdao University Qingdao ChinaDepartment of Materials the Affiliated Qingdao Municipal Hospital of Qingdao University Qingdao ChinaDepartment of Nephrology the Affiliated Qingdao Municipal Hospital of Qingdao University Qingdao ChinaDepartment of Nephrology the Affiliated Qingdao Municipal Hospital of Qingdao University Qingdao ChinaDepartment of Nephrology the Affiliated Qingdao Municipal Hospital of Qingdao University Qingdao ChinaDepartment of Nephrology the Affiliated Qingdao Municipal Hospital of Qingdao University Qingdao ChinaDepartment of Nephrology the Affiliated Qingdao Municipal Hospital of Qingdao University Qingdao ChinaDepartment of Ultrasound the Affiliated Qingdao Municipal Hospital of Qingdao University Qingdao ChinaDepartment of Nephrology the Affiliated Qingdao Municipal Hospital of Qingdao University Qingdao ChinaAbstract Background X‐linked Alport syndrome (XLAS) is an inherited renal disease caused by rare variants of COL4A5 on chromosome Xq22. Many studies have indicated that single nucleotide variants (SNVs) in exons can disrupt normal splicing process of the pre‐mRNA by altering various splicing regulatory signals. The male patients with XLAS have a strong genotype–phenotype correlation. Confirming the effect of variants on splicing can help to predict kidney prognosis. This study aimed to investigate whether single nucleotide substitutions, located within three bases at the 5′ end of the exons or internal position of the exons in COL4A5 gene, cause aberrant splicing process. Methods We analyzed 401 SNVs previously presumed missense and nonsense variants in COL4A5 gene by bioinformatics programs and identified candidate variants that may affect the splicing of pre‐mRNA via minigene assays. Results Our study indicated three of eight candidate variants induced complete or partial exon skipping. Variants c.2678G>C and c.2918G>A probably disturb classic splice sites leading to corresponding exon skipping. Variant c.3700C>T may disrupt splicing enhancer motifs accompanying with generation of splicing silencer sequences resulting in the skipping of exon 41. Conclusion Our study revealed that two missense variants positioned the first nucleotides of the 5′ end of COL4A5 exons and one internal exonic nonsense variant caused aberrant splicing. Importantly, this study emphasized the necessity of assessing the effects of SNVs at the mRNA level.https://doi.org/10.1002/mgg3.2395Alport syndromeCOL4A5exon splicingexonic variantminigene analysis |
| spellingShingle | Ran Zhang Yanhua Lang Xiaomeng Shi Yiyin Zhang Xuyan Liu Fengjiao Pan Dan Qiao Xin Teng Leping Shao Three exonic variants in the COL4A5 gene alter RNA splicing in a minigene assay Molecular Genetics & Genomic Medicine Alport syndrome COL4A5 exon splicing exonic variant minigene analysis |
| title | Three exonic variants in the COL4A5 gene alter RNA splicing in a minigene assay |
| title_full | Three exonic variants in the COL4A5 gene alter RNA splicing in a minigene assay |
| title_fullStr | Three exonic variants in the COL4A5 gene alter RNA splicing in a minigene assay |
| title_full_unstemmed | Three exonic variants in the COL4A5 gene alter RNA splicing in a minigene assay |
| title_short | Three exonic variants in the COL4A5 gene alter RNA splicing in a minigene assay |
| title_sort | three exonic variants in the col4a5 gene alter rna splicing in a minigene assay |
| topic | Alport syndrome COL4A5 exon splicing exonic variant minigene analysis |
| url | https://doi.org/10.1002/mgg3.2395 |
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