title: HRAS mutation analysis in Costello syndrome: genotype and phenotype correlation.
abstract: 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.
authors.affiliation: Division of Medical Genetics, A. I. duPont Hospital for Children, Wilmington, DE 19899, USA. kgripp@nemours.org
authors.forename: Karen W
authors.initials: KW
authors.lastname: Gripp
authors.forename: Angela E
authors.initials: AE
authors.lastname: Lin
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Stabley
authors.forename: Linda
authors.initials: L
authors.lastname: Nicholson
authors.forename: Charles I
authors.initials: CI
authors.lastname: Scott
authors.forename: Daniel
authors.initials: D
authors.lastname: Doyle
authors.forename: Yoko
authors.initials: Y
authors.lastname: Aoki
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Matsubara
authors.forename: Elaine H
authors.initials: EH
authors.lastname: Zackai
authors.forename: Pablo
authors.initials: P
authors.lastname: Lapunzina
authors.forename: Antonio
authors.initials: A
authors.lastname: Gonzalez-Meneses
authors.forename: Jennifer
authors.initials: J
authors.lastname: Holbrook
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Agresta
authors.forename: Iris L
authors.initials: IL
authors.lastname: Gonzalez
authors.forename: Katia
authors.initials: K
authors.lastname: Sol-Church
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D018376:Cardiovascular Abnormalities / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005145:Face / Q000002:abnormalities; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000473:pathology; D008297:Male; D009139:Musculoskeletal Abnormalities / Q000473:pathology; D020125:Mutation, Missense; D009369:Neoplasms / Q000235:genetics; D010641:Phenotype; D012868:Skin Abnormalities / Q000473:pathology; D013577:Syndrome