TY - JOUR
T1 - HRAS mutation analysis in Costello syndrome
T2 - Genotype and phenotype correlation
AU - Gripp, Karen W.
AU - Lin, Angela E.
AU - Stabley, Deborah L.
AU - Nicholson, Linda
AU - Scott, Charles I.
AU - Doyle, Daniel
AU - Aoki, Yoko
AU - Matsubara, Yoichi
AU - Zackai, Elaine H.
AU - Lapunzina, Pablo
AU - Gonzalez-Meneses, Antonio
AU - Holbrook, Jennifer
AU - Agresta, Cynthia A.
AU - Gonzalez, Iris L.
AU - Sol-Church, Katia
PY - 2006/1/1
Y1 - 2006/1/1
N2 - 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.
AB - 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.
KW - Bladder cancer
KW - Gain-of-function
KW - HRAS
KW - Over-growth syndrome
KW - Rhabdomyosarcoma
UR - https://www.scopus.com/pages/publications/30144433531
U2 - 10.1002/ajmg.a.31047
DO - 10.1002/ajmg.a.31047
M3 - Article
C2 - 16329078
AN - SCOPUS:30144433531
SN - 1552-4825
VL - 140 A
SP - 1
EP - 7
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 1
ER -