The recurrent PPP1CB mutation p.Pro49Arg in an additional Noonan-like syndrome individual: Broadening the clinical phenotype

Am J Med Genet A. 2017 Mar;173(3):824-828. doi: 10.1002/ajmg.a.38070.


We report on a 12-year-old Brazilian boy with the p.Pro49Arg mutation in PPP1CB, a novel gene associated with RASopathies. This is the fifth individual described, and the fourth presenting the same variant, suggesting a mutational hotspot. Phenotypically, he also showed the same hair pattern-sparse, thin, and with slow growing-, similar to the typical ectodermal finding observed in Noonan syndrome-like disorder with loose anagen hair. Additionally, he presented craniosynostosis, a rare clinical finding in RASopathies. This report gives further support that this novel RASopathy-PPP1CB-related Noonan syndrome with loose anagen hair-shares great similarity to Noonan syndrome-like disorder with loose anagen hair, and expands the phenotypic spectrum by adding the cranial vault abnormality. © 2017 Wiley Periodicals, Inc.

Keywords: Noonan syndrome-like disorder with loose anagen hair; PPP1CB; PPP1CB-related Noonan syndrome with loose anagen hair; RASopathies; craniosynostosis.

Publication types

  • Letter
  • Review

MeSH terms

  • Amino Acid Substitution*
  • Brazil
  • Child
  • Codon*
  • Genetic Association Studies
  • Humans
  • Male
  • Mutation*
  • Mutation, Missense
  • Noonan Syndrome / diagnosis*
  • Noonan Syndrome / genetics*
  • Phenotype*
  • Protein Phosphatase 1 / genetics*


  • Codon
  • PPP1CB protein, human
  • Protein Phosphatase 1