Nature Genetics online: December 11, 2011
Mutations at a single codon in Mad homology 2 domain of SMAD4 cause Myhre syndrome
Carine Le Goff, Clémentine Mahaut, Avinash Abhyankar, Wilfried Le Goff, Valérie Serre, Alexandra Afenjar, Anne Destrée, Maja di Rocco, Delphine Héron, Sébastien Jacquemont, Sandrine Marlin, Marleen Simon, John Tolmie, Alain Verloes, Jean-Laurent Casanova, Arnold Munnich and Valérie Cormier-Daire
Using exome sequencing of individuals with Myhre syndrome, we identified SMAD4 as a candidate gene that contributes to this syndrome on the basis of its pivotal role in the bone morphogenetic pathway (BMP) and transforming growth factor (TGF)-β signaling. We identified three distinct heterozygous missense SMAD4 mutations affecting the codon for Ile500 in 11 individuals with Myhre syndrome.