HRAS mutation analysis in Costello syndrome: genotype and phenotype correlation.
Gripp KW,
Lin AE,
Stabley DL,
Nicholson L,
Scott CI Jr,
Doyle D,
Aoki Y,
Matsubara Y,
Zackai EH,
Lapunzina P,
Gonzalez-Meneses A,
Holbrook J,
Agresta CA,
Gonzalez IL,
Sol-Church K.
Division of Medical Genetics, A. I. duPont Hospital for Children, Wilmington, DE 19899, USA. kgripp@nemours.org
Costello syndrome is a rare condition comprising mental retardation, distinctive facial appearance, cardiovascular abnormalities (typically pulmonic stenosis, hypertrophic cardiomyopathy, and/or atrial tachycardia), tumor predisposition, and skin and musculoskeletal abnormalities. Recently mutations in HRAS were identified in 12 Japanese and Italian patients with clinical information available on 7 of the Japanese patients. To expand the molecular delineation of Costello syndrome, we performed mutation analysis in 34 North American and 6 European (total 40) patients with Costello syndrome, and detected missense mutations in HRAS in 33 (82.5%) patients. 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. In two patients, we found a mutation resulting in an alanine substitution in position 12 (G12A), and in one patient, we detected a novel mutation (G13C). Five different HRAS mutations have now been reported in Costello syndrome, however genotype-phenotype correlation remains incomplete. (c) 2005 Wiley-Liss, Inc.
PMID: 16329078 [PubMed - indexed for MEDLINE]