Providing more evidence on LZTR1 variants in Noonan syndrome patients

Josefina Chinton, Victoria Huckstadt, Mafalda Mucciolo, Francesca Lepri, Antonio Novelli, Luis Pablo Gravina, María Gabriela Obregon

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)409-414
Number of pages6
JournalAmerican Journal of Medical Genetics, Part A
Volume182
Issue number2
DOIs
Publication statusE-pub ahead of print - 2019

Keywords

  • Argentina
  • LZTR1
  • Noonan syndrome
  • RASopathies

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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