title: A lethal course of hypertrophic cardiomyopathy in Noonan syndrome due to a novel germline mutation in the KRAS gene: case study.
abstract: Noonan syndrome is a relatively common and heterogeneous genetic disorder, including congenital heart defect in more than half of the cases. If the defect is not large, life expectancy is normal. Here we report on a case of an infant with Noonan syndrome and rapidly progressive hypertrophic cardiomyopathy with lethal outcome, in whom we identified a novel mutation in the KRAS gene. This heterozygous unclassified missense variant in exon 3: c.179G> T (p.Gly60Val) might be associated with a lethal form of Noonan syndrome. The malignant clinical course of the disease and the lethal outcome in an infant only a few months old might be connected to RAS-mitogen-activated protein kinase pathway hyperactivation, consequently promoting cell growth and proliferation, leading to rapidly progressive hypertrophic cardiomyopathy. Further biochemical and functional studies are needed to confirm this hypothesis.
authors.forename: Gregor
authors.initials: G
authors.lastname: Nosan
authors.forename: Sara
authors.initials: S
authors.lastname: Bertok
authors.forename: Samo
authors.initials: S
authors.lastname: Vesel
authors.forename: Helger G
authors.initials: HG
authors.lastname: Yntema
authors.affiliation: Darja Paro-Panjan, Department of Neonatology, Division of Pediatrics, University Medical Centre Ljubljana, Bohoriceva ulica 20, 1000 Ljubljana, Slovenia, darja.paro@kclj.si.
authors.forename: Darja
authors.initials: D
authors.lastname: Paro-Panjan
mesh_terms: D000818:Animals; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics*; D005091:Exons / Q000235:genetics; D017809:Fatal Outcome; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D007223:Infant; D008297:Male; D020125:Mutation, Missense; D009634:Noonan Syndrome / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins