Using a machine learning model, researchers have shown in a recent study that, depending on the position of mutations, variants of the SRCAP gene do not only cause Floating Harbor syndrome but also other neurogenetic disorders. SRCAP encodes the Snf2-related CREBBP activator protein, an ATPase involved in chromatin remodelling by regulating incorporation of histones into nucleosomes. It has been known that de novo mutations specifically located in exons 33 or 34 of SRCAP result in Floating Harbor syndrome (FLHS), a rare neurodevelopmental disorder mainly characterized by short stature, speech delay and very specific facial dysmorphism.

In the study led by groups from Canada and the Netherlands, the researchers investigated a cohort of 33 individuals with clinical features distinct from FLHS and with truncating, mostly de novo, mutations located at different sites in SRCAP outside the known FLHS-causing locus. In FLHS, a very specific pattern of DNA methylation changes is found in blood and the researchers explored whether the patients in their cohort also showed a distinct signature. They detected a clear relationship between variant position, resulting DNA methylation profile and clinical phenotype.

The study results have been published in the American Journal of Human Genetics.