title: Constitutional NRAS mutations are rare among patients with Noonan syndrome or juvenile myelomonocytic leukemia.
abstract: Recently, germline mutations of NRAS have been shown to be associated with Noonan syndrome (NS), a relatively common developmental disorder characterized by short stature, congenital heart disease, and distinctive facial features. We report on the mutational analysis of NRAS in a cohort of 125 French patients with NS and no known mutation for PTPN11, KRAS, SOS1, MEK1, MEK2, RAF1, BRAF, and SHOC2. The c.179G>A (p.G60E) mutation was identified in two patients with typical NS, confirming that NRAS germline mutations are a rare cause of this syndrome. We also screened our cohort of 95 patients with juvenile myelomonocytic leukemia (JMML). Among 17 patients with NRAS-mutated JMML, none had clinical features suggestive of NS. None of the 11 JMML patients for which germline DNA was available had a constitutional NRAS mutation.
authors.affiliation: Department of Genetics, AP-HP-Robert Debré Hospital, Paris, France.
authors.forename: Lilia
authors.initials: L
authors.lastname: Kraoua
authors.forename: Hubert
authors.initials: H
authors.lastname: Journel
authors.forename: Philippe
authors.initials: P
authors.lastname: Bonnet
authors.forename: Jeanne
authors.initials: J
authors.lastname: Amiel
authors.forename: Nathalie
authors.initials: N
authors.lastname: Pouvreau
authors.forename: Clarisse
authors.initials: C
authors.lastname: Baumann
authors.forename: Alain
authors.initials: A
authors.lastname: Verloes
authors.forename: Hélène
authors.initials: H
authors.lastname: Cavé
mesh_terms: D000293:Adolescent; D004252:DNA Mutational Analysis; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D018095:Germ-Line Mutation; D006801:Humans; D007223:Infant; D054429:Leukemia, Myelomonocytic, Juvenile / Q000235:genetics*; D008297:Male; D009634:Noonan Syndrome / Q000235:genetics*