In addition to contributing significantly to the development of many human cancers through somatic mutations, germline pathogenic variants in genes encoding members of the RAS/MAPK pathway cause a complex group of Mendelian disorders known as RASopathies. This pathway plays an indispensable role in normal cellular processes ranging from proliferation to metabolism. Manifestations of RASopathies range from increased nuchal translucency to postnatal neurodevelopmental disorders.

Genetic diagnosis of RASopathies requires a comprehensive approach because of the large number of underlying genes and the difficulty in distinguishing phenotypes between syndromes associated with RASopathies. Current genetic diagnostic techniques, including next-generation sequencing using targeted genome or whole-exome/whole-genome sequencing, have improved genetic diagnosis. However, due to the complexity of the RAS/MAPK pathway, there are still significant challenges in the interpretation of variants of unknown significance. The treatment of RASopathy is a hot topic due to the large number of patients affected worldwide.

This Methods Collection aims to highlight current and innovative approaches related to RASopathies, ranging from tools for functional assessment of rare variants that pose a significant challenge for genetic diagnosis to treatment options.