Professor Karen Gripp and his team from DuPont Hospital studied genetic mutations in H-ras gene which lead to Costello Syndrome, scientists found that the gene mutation occured in germline cells though it was not observed in the genotype of the parents of the affected patients. The researchers have published the results of their study in Wiley Interscience. The researchers identified mutations in codon 12 or 13 in the H-ras gene in 85% patients. The authors feel that the identification of these mutations in combination with the knowledge from cancer research on HRAS and the MAPK pathway will allow for the use of medications directed at this pathway.
Costello Syndrome is very rare, with only 150 cases reported worldwide. It is associated with mental retardation, distinctive facial characteristics, cardiovascular abnormalities, and a predisposition for tumors. Patients often develop soft tissue tumors in childhood and bladder cancer as young adults. The researchers extracted DNA from blood, saliva or cell lines and performed DNA sequencing. When possible, they also sequenced the genes of the patients' parents. The nature of the missense mutations, along with the paternal age effect observed in Costello syndrome suggests a paternal origin of the mutations, the researchers report.