| Literature DB >> 29255276 |
Marine Legendre1,2, Montserrat Rodriguez-Ballesteros1, Massimiliano Rossi3, Véronique Abadie4, Jeanne Amiel5, Nicole Revencu6, Patricia Blanchet7, Frédéric Brioude8, Marie-Ange Delrue9, Yassamine Doubaj10, Abdelaziz Sefiani10, Christine Francannet11, Muriel Holder-Espinasse12, Pierre-Simon Jouk13, Sophie Julia14, Judith Melki15, Sébastien Mur16, Sophie Naudion9, Jennifer Fabre-Teste17, Tiffany Busa18, Stephen Stamm19, Stanislas Lyonnet5, Tania Attie-Bitach5, Alain Kitzis1,2, Brigitte Gilbert-Dussardier1,2, Frédéric Bilan20,21.
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.Entities:
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Year: 2017 PMID： 29255276 PMCID： PMC5839049 DOI： 10.1038/s41431-017-0007-0
Source DB: PubMed Journal: Eur J Hum Genet ISSN： 1018-4813 Impact factor: 4.246