Providing more evidence on LZTR1 variants in Noonan syndrome patients: American Journal of Medical Genetics, Part A

J. Chinton, V. Huckstadt, M. Mucciolo, F. Lepri, A. Novelli, L.P. Gravina, M.G. Obregon

Research output: Contribution to journalArticlepeer-review


Noonan syndrome (NS, OMIM 163950) is a common autosomal dominant RASopathy caused mainly by gain-of-function germline pathogenic variants in genes involved in the RAS/MAPK signaling pathway. LZTR1 gene has been associated with both dominant and recessive NS. Here, we present seven patients with NS and variants in the LZTR1 gene from seven unrelated families, 14 individuals in total. The detection rAte of LZTR1 variants in our NS cohort was 4% similar to RAF1 and KRAS genes, indicating that variants in this gene might be frequent among our population. Three different variants were detected, c.742G>A (p.Gly248Arg), c.360C>A (p.His120Gln), and c.2245T>C (p.Tyr749His). The pathogenic variant c.742G>A (p.Gly248Arg) was found in five/seven patients. In our cohort 50% of patients presented heart defects and neurodevelopment delay or learning disabilities, short stature was present in 21% of them and one patient had acute lymphoblastic leukemia. This study broadens the spectrum of variants in the LZTR1 gene and provides increased knowledge of the clinical phenotypes observed in Argentinean NS patients. © 2019 Wiley Periodicals, Inc.
Original languageEnglish
Pages (from-to)409-414
Number of pages6
JournalAm. J. Med. Genet. Part A
Issue number2
Publication statusPublished - 2020


  • Argentina
  • LZTR1
  • Noonan syndrome
  • RASopathies
  • protein tyrosine phosphatase SHP 2
  • Raf protein
  • KRAS protein, human
  • LZTR1 protein, human
  • protein p21
  • Raf1 protein, human
  • transcription factor
  • acute lymphoblastic leukemia
  • adult
  • Argentinian
  • Article
  • clinical article
  • clinical feature
  • congenital heart malformation
  • controlled study
  • developmental delay
  • dominant inheritance
  • face dysmorphia
  • female
  • gene
  • gene frequency
  • gene identification
  • gene segregation
  • heart atrium septum defect
  • heart ventricle septum defect
  • heterozygosity
  • human
  • hypertelorism
  • hypertrophic cardiomyopathy
  • infant
  • learning disorder
  • LZTR1 gene
  • macrocephaly
  • male
  • micrognathia
  • missense mutation
  • next generation sequencing
  • oncogene K ras
  • patent ductus arteriosus
  • pathogenesis
  • priority journal
  • ptosis (eyelid)
  • PTPN11 gene
  • pulmonary valve stenosis
  • RAF1 gene
  • Sanger sequencing
  • sequence alignment
  • sequence analysis
  • short stature
  • South America
  • adolescent
  • child
  • facies
  • genetic predisposition
  • genetics
  • middle aged
  • mutation
  • pathology
  • pedigree
  • phenotype
  • preschool child
  • young adult
  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Facies
  • Female
  • Genetic Predisposition to Disease
  • Heart Defects, Congenital
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Mutation
  • Noonan Syndrome
  • Pedigree
  • Phenotype
  • Proto-Oncogene Proteins c-raf
  • Proto-Oncogene Proteins p21(ras)
  • Transcription Factors
  • Young Adult


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