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.
A previous genetic study of 12 Japanese and Italian patients with Costello syndrome found mutations in the HRAS gene sequence. To confirm this connection and expand the understanding of the possible cause of Costello syndrome, researchers, led by Karen W. Gripp of A. I. DuPont Hospital for Children in Wilmington, Delaware, performed mutation analyses on 40 North American and European patients.
The researchers identified patients with the syndrome through affiliated organizations and physician referral. They extracted DNA from blood, saliva or cell lines and performed DNA sequencing. When possible, they also sequenced the genes of the patients' parents.
The results were striking. Among the patients with Costello syndrome, "We detected missense mutations in HRAS in 33 (82.5%) patients," the authors report. "All mutations affected either codon 12 or 13 of the protein product, with G12S occurring in 30 (90.9%) patients of the mutation-positive cases."
The researchers reviewed the clinical presentation of the patients who did not have HRAS mutation and found inconsistencies in their facial characteristics. They suggest that these patients m
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