HRAS and the Costello syndrome

Research output: Contribution to journalReview article

76 Scopus citations

Abstract

Costello syndrome (CS) is a complex developmental disorder involving characteristic craniofacial features, failure to thrive, developmental delay, cardiac and skeletal anomalies and a predisposition to develop neoplasia, both benign and malignant. CS is caused by activating germline mutations in HRAS and belongs to an exciting class of genetic syndromes that are caused by perturbation of function through the Ras pathway. Some of these other syndromes include Noonan syndrome, LEOPARD syndrome, neurofibromatosis 1 and cardio-facio-cutaneous syndrome. Ras is a critical signaling hub in the cell and is activated by receptor tyrosine kinases, G-protein-coupled receptors, cytokine receptors and extracellular matrix receptors. The downstream effectors of Ras are many and control vital cellular functions including cell cycle progression, cell survival, motility, transcription, translation and membrane trafficking. Understanding the genetic etiology of CS is the first step in gaining insight to the role Ras plays in human development, cellular signaling and cancer pathogenesis.

Original languageEnglish (US)
Pages (from-to)101-108
Number of pages8
JournalClinical Genetics
Volume71
Issue number2
DOIs
StatePublished - Feb 2007
Externally publishedYes

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Keywords

  • Cardio-facio-cutaneous syndrome
  • Costello syndrome
  • Genotype-phenotype correlation
  • Germline mutation
  • HRAS mutations
  • Loss of heterozygosity
  • Mosaicism
  • Ras pathway
  • Rhabdomyosarcoma

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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