Disruption of Friend of GATA 2 gene (FOG-2) by a de novo t(8;10) chromosomal translocation is associated with heart defects and gonadal dysgenesis

FOG-2 (Friend of Gata 2) is a transcriptional co-factor able to differentially regulate the expression of GATA-target genes in different promoter contexts. Mouse models evidenced that FOG-2 plays a role in congenital heart disease and normal testis development. In human, while FOG-2 mutations have been identified in sporadic cases of tetralogy of Fallot, no mutations are described to be associated with impaired gonadal function. We here describe a young boy with a balanced t(8;10)(q23.1;q21.1) translocation who was born with congenital secundum-type atrial septal defect and gonadal dysgenesis. FISH mapped the chromosome 8 translocation breakpoint to within the IVS4 of the FOG-2 gene, whereas the chromosome 10 breakpoint was found to lie in a desert gene region. Quantitative analysis of FOG-2 expression revealed the presence of a truncated transcript, but there was no detectable change in the expression of the genes flanking the 10q breakpoint, thus making it possible to assign the observed clinical phenotype to altered FOG2 expression. Genetic and clinical analyses provide insights into the signalling pathways by which FOG-2 affects not only cardiac development but also gonadal function and its preservation.