The RASopathies: Developmental syndromes of Ras/MAPK pathway dysregulation

By W. E. Tidyman, K. Rauen. Current Opinion in Genetics and Development, 2009

760 citations recorded by the source corpus.

The Ras/mitogen activated protein kinase (MAPK) pathway is essential in the regulation of the cell cycle, differentiation, growth and cell senescence, all of which are critical to normal development. It is therefore not surprising that its dysregulation has profound effects on development. A class of developmental disorders, the “RASopathies”, is caused by germline mutations in genes that encode protein components of the Ras/MAPK pathway. The vast majority of these mutations result in increased signal transduction down the Ras/MAPK pathway, but usually to a lesser extent than somatic mutations associated with oncogenesis. Each syndrome exhibits unique phenotypic features, however, since they all cause dysregulation of the Ras/MAPK pathway, there are numerous overlapping phenotypic features between the syndromes, including characteristic facial features, cardiac defects, cutaneous abnormalities, neurocognitive delay and a predisposition to malignancies. Here we review the clinical and underlying molecular basis for each of these syndromes.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/de1d87865947e3d979d40b6fe7907f5322ab180a

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Citations in the corpus

• A comprehensive survey of Ras mutations in cancer (2012, neutral): “germline mutations of each isoform generate overlapping but distinctive sets of neuro-cardio-facial proliferative disorders (53).”
• Ras superfamily GEFs and GAPs: validated and tractable targets for cancer therapy? (2010, background): “Therefore, similar to other mutations found in developmental syndromes that activate KRAS, RAF1 (also known as CRAF), MEK1 (also known as MAPKK1) and MEK2 (also known as MAPKK2), the SOS1 mutations are weakly activating and might not be potent enough to cause cance”
• The MAPK cascades: signaling components, nuclear roles and mechanisms of nuclear translocation. (2011, background): “On the other hand, when dysregulated, this cascade plays a major role in various pathologies, inducing neurodegenerative diseases [21], developmental diseases [22], diabetes [23], and particularly notable — cancer [24,25].”