| Autor: |
Xing, Lv, Wei-Qing, Wu, Jia-Xun, Zhang, Liu-Fei, Miao, Bai-Zeng, Yu, Fang-Fang, Chen, Ying-Xia, Cui, Zheng-Kun, Xia, Zhi-Hong, Liu, Xiao-Jun, Li |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
Cytogenetic and genome research. 160(5) |
| ISSN: |
1424-859X |
| Popis: |
X-linked Alport syndrome (XLAS) is a common hereditary nephropathy caused by COL4A5 gene mutations. To date, many splice site mutations have been described but few have been functionally analyzed to verify the exact splicing effects that contribute to disease pathogenesis. Here, we accidentally discovered 2 COL4A5 gene splicing mutations affecting the same residue (c.2917+1GA and c.2917+1GC) in 2 unrelated Chinese families. In vitro minigene assays showed that the 2 mutations produced 3 transcripts in H293T cells: one with a 96-bp deletion in exon 33, one with exon 33 skipping, and one with exon 33-34 skipping. However, fragment analysis results showed that the main splicing effects of the 2 mutations were different, the c.2917+1GA mutation mainly activated a cryptic donor splice site in exon 33 and resulted in the deletion of 96 bp in exon 33, while the c.2917+1GC mutation mainly caused exon 33 skipping. Our findings indicate that different nucleotide substitutions at the same residue can cause different splicing effects, which may contribute to the variable phenotype of Alport syndrome. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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