AI Article Synopsis
- - CHARGE syndrome is a rare genetic disorder primarily caused by mutations in the CHD7 gene, often occurring as de novo mutations.
- - The study identifies a specific area with recurrent mutations in the CHD7 gene, highlighting a particular genomic context that makes these mutations impactful, including issues with natural acceptor sites.
- - By using computational analysis and experimental methods, the research shows that these mutations create new splice sites, suggesting that combining different diagnostic techniques could improve molecular diagnosis in patients.
Article Abstract
CHARGE syndrome is a rare genetic disorder mainly due to de novo and private truncating mutations of CHD7 gene. Here we report an intriguing hot spot of intronic mutations (c.5405-7G > A, c.5405-13G > A, c.5405-17G > A and c.5405-18C > A) located in CHD7 IVS25. Combining computational in silico analysis, experimental branch-point determination and in vitro minigene assays, our study explains this mutation hot spot by a particular genomic context, including the weakness of the IVS25 natural acceptor-site and an unconventional lariat sequence localized outside the common 40 bp upstream the acceptor splice site. For each of the mutations reported here, bioinformatic tools indicated a newly created 3' splice site, of which the existence was confirmed using pSpliceExpress, an easy-to-use and reliable splicing reporter tool. Our study emphasizes the idea that combining these two complementary approaches could increase the efficiency of routine molecular diagnosis.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5839049 | PMC |
| http://dx.doi.org/10.1038/s41431-017-0007-0 | DOI Listing |
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