Germline mutations in HRAS proto-oncogene cause Costello syndrome

Nat Genet. 2005 Oct;37(10):1038-40. doi: 10.1038/ng1641. Epub 2005 Sep 18.

Abstract

Costello syndrome is a multiple congenital anomaly and mental retardation syndrome characterized by coarse face, loose skin, cardiomyopathy and predisposition to tumors. We identified four heterozygous de novo mutations of HRAS in 12 of 13 affected individuals, all of which were previously reported as somatic and oncogenic mutations in various tumors. Our observations suggest that germline mutations in HRAS perturb human development and increase susceptibility to tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Amino Acid Sequence
  • Cardiomyopathies / genetics
  • Face / abnormalities
  • Female
  • Genetic Predisposition to Disease*
  • Germ-Line Mutation*
  • Humans
  • Intellectual Disability / genetics*
  • Molecular Sequence Data
  • Neoplasms / genetics
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Skin Abnormalities / genetics
  • Syndrome

Substances

  • HRAS protein, human
  • Proto-Oncogene Proteins p21(ras)

Associated data

  • OMIM/163950
  • OMIM/218040
  • RefSeq/NC_000001
  • RefSeq/NC_000011
  • RefSeq/NC_000012
  • RefSeq/NC_000023
  • RefSeq/NM_005343