TY - JOUR
T1 - CHARGE syndrome
T2 - A recurrent hotspot of mutations in CHD7 IVS25 analyzed by bioinformatic tools and minigene assays /631/208 /692/308 brief-communication
AU - Legendre, Marine
AU - Rodriguez-Ballesteros, Montserrat
AU - Rossi, Massimiliano
AU - Abadie, Véronique
AU - Amiel, Jeanne
AU - Revencu, Nicole
AU - Blanchet, Patricia
AU - Brioude, Frédéric
AU - Delrue, Marie Ange
AU - Doubaj, Yassamine
AU - Sefiani, Abdelaziz
AU - Francannet, Christine
AU - Holder-Espinasse, Muriel
AU - Jouk, Pierre Simon
AU - Julia, Sophie
AU - Melki, Judith
AU - Mur, Sébastien
AU - Naudion, Sophie
AU - Fabre-Teste, Jennifer
AU - Busa, Tiffany
AU - Stamm, Stephen
AU - Lyonnet, Stanislas
AU - Attie-Bitach, Tania
AU - Kitzis, Alain
AU - Gilbert-Dussardier, Brigitte
AU - Bilan, Frédéric
N1 - Publisher Copyright:
© 2017 European Society of Human Genetics.
PY - 2018/2/1
Y1 - 2018/2/1
N2 - 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.
AB - 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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U2 - 10.1038/s41431-017-0007-0
DO - 10.1038/s41431-017-0007-0
M3 - Article
C2 - 29255276
AN - SCOPUS:85038399503
SN - 1018-4813
VL - 26
SP - 287
EP - 292
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 2
ER -