WEB Costello Syndrome Linked to HRAS Mutation
Rare Condition Linked to Cell Growth Gene
WEB Costello syndrome (CS), a rare genetic condition characterized by overgrowth, facial and skeletal abnormalities, and intellectual disability, has been linked to germline mutations in the gene HRAS. HRAS encodes a small GTPase involved in the Ras-mitogen activated protein kinase (MAPK) signaling pathway, which plays a crucial role in cell growth and proliferation.
Unraveling the Genetic Basis of CS
Using a combination of whole-exome sequencing and targeted mutation analysis, researchers at the University of Washington School of Medicine identified mutations in HRAS in 55 individuals with CS. Germline mutations were found in 41 individuals, while somatic mutations were identified in 14 individuals. These mutations were present in highly conserved regions of HRAS, suggesting their functional importance.
Further studies revealed that the HRAS mutations found in CS patients led to the activation of the MAPK pathway, resulting in increased cell growth and proliferation. This activation was shown to be specific to HRAS mutations, as mutations in other genes in the MAPK pathway did not produce similar effects.
Implications for Diagnosis and Treatment
The identification of HRAS mutations as the genetic basis for CS has significant implications for diagnosis and treatment. It provides a molecular target that can be used to develop genetic tests for CS, allowing for earlier and more accurate diagnosis. Moreover, the understanding of the role of HRAS in the pathogenesis of CS could lead to the development of novel therapeutic strategies.
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