Artigo Acesso aberto Revisado por pares

CHARGE syndrome: a recurrent hotspot of mutations in CHD7 IVS25 analyzed by bioinformatic tools and minigene assays

2017; Springer Nature; Volume: 26; Issue: 2 Linguagem: Inglês

10.1038/s41431-017-0007-0

ISSN

1476-5438

Autores

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

Tópico(s)

Salivary Gland Tumors Diagnosis and Treatment

Resumo

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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