RAF1 variant in a patient with Noonan syndrome with multiple lentigines and craniosynostosis

Am J Med Genet A. 2019 Aug;179(8):1598-1602. doi: 10.1002/ajmg.a.61203. Epub 2019 May 30.

Abstract

We report the case of a 14 years and 8 months girl, who is the first child of nonconsanguineous parents, with short stature, obstructive hypertrophic cardiomyopathy, multiple facial lentigines, high and wide forehead, downslanting palpebral fissures, low-set ears, short neck, and pectus excavatum; all features suggestive of Noonan syndrome with multiple lentigines (NSML). In addition, the patient exhibited craniosynostosis. Molecular analysis of rats sarcoma (RAS)/mitogen-activated protein kinase (MAPK) pathway genes with high-resolution melting curve analysis followed by sequencing showed a RAF1 amino acid substitution of valine to glycine at position 263 (p.V263G). The present report provides clinical data regarding the first association of a RAF1 variant and craniosynostosis in a patient with clinical diagnosis of NSML.

Keywords: RAF1 mutations; Noonan syndrome with multiple lentigines; craniosynostosis.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Alleles
  • Amino Acid Substitution
  • Craniosynostoses / diagnosis*
  • Craniosynostoses / genetics*
  • Exons
  • Facies
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genetic Variation*
  • Humans
  • LEOPARD Syndrome / diagnosis*
  • LEOPARD Syndrome / genetics*
  • Mutation
  • Phenotype*
  • Proto-Oncogene Proteins c-raf / genetics*

Substances

  • Proto-Oncogene Proteins c-raf
  • Raf1 protein, human