One of the latest published articles in Nature inquires the unexplored role of de novo mutations in regulatory elements affecting genes associated with developmental disorders or other genes. Therefore, the authors identify de novo mutations in three classes of putative regulatory elements in almost 8.000 patients with developmental disorders.

These almost 8000 (7930) patients are individuals with severe, undiagnosed developmental disorder, and their parents to the Deciphering Developmental Disorders (DDD) study from clinical genetics centers in the UK and Ireland.

In this study, they estimate that, genome wide, 1-3% of patients without a diagnostic coding variant carry pathogenic de novo mutations in fetal brain-active regulatory elements and that only 0.15% of all possible mutations within highly conserved fetal brain-active elements cause neurodevelopmental disorders within a dominant mechanism.

In conclusion, the results emphasize the importance of combining functional and evolutionary evidence to identify regulatory causes of genetic disorders.

Sequencing and phenotype data are available in the European Genome-phenome Archive (EGA) under the study number EGAS00001000775