A postzygotic mutation in RHOA has been identified as the genetic cause of a distinct mosaic disorder in humans. RHOA is a member of the Rho family of GTPases, which have many roles in coordinating fundamental cellular processes including cell adhesion, migration and proliferation. RHOA can stimulate the formation of actin stress fibers and focal adhesions and is a key protein in the regulation of changes in the actin cytoskeleton in various tissues.

In a recently published study with major contribution by the Institute of Human Genetics at the University Medical Center Göttingen, the web-based platform GeneMatcher brought together international research groups investigating four patients with a similar phenotype. The affected individuals showed hypopigmentation of the skin, dental anomalies, body asymmetry, and limb length discrepancy as well as brain magnetic resonance imaging (MRI) anomalies. In their genetic studies, the researchers performed whole-exome and ultra-deep amplicon sequencing and compared data generated from samples of both, affected and unaffected areas of the skin. As a result, they discovered the identical postzygotic missense variant of the RHOA gene in all four patients. In silico analysis indicated that this variant causes a specific change in RHOA interaction with downstream effectors and thus impairs signaling activation.

The results of the study have been published in Human Mutation.