CHARGE syndrome: A recurrent hotspot of mutations in CHD7 IVS25 analyzed by bioinformatic tools and minigene assays /631/208 /692/308 brief-communication

Marine Legendre, Montserrat Rodriguez-Ballesteros, Massimiliano Rossi, Véronique Abadie, Jeanne Amiel, Nicole Revencu, Patricia Blanchet, Frédéric Brioude, Marie Ange Delrue, Yassamine Doubaj, Abdelaziz Sefiani, Christine Francannet, Muriel Holder-Espinasse, Pierre Simon Jouk, Sophie Julia, Judith Melki, Sébastien Mur, Sophie Naudion, Jennifer Fabre-Teste, Tiffany BusaStephen Stamm, Stanislas Lyonnet, Tania Attie-Bitach, Alain Kitzis, Brigitte Gilbert-Dussardier, Frédéric Bilan

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


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.

Original languageEnglish
Pages (from-to)287-292
Number of pages6
JournalEuropean Journal of Human Genetics
Issue number2
StatePublished - Feb 1 2018

Bibliographical note

Publisher Copyright:
© 2017 European Society of Human Genetics.

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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