title: Clinical and molecular analysis of RASopathies in a group of Turkish patients.
abstract: The 'RASopathies' are a group of disorders sharing many clinical features and a common pathophysiology. In this study, we aimed to clinically evaluate a group of Turkish patients and elucidate the underlying genetic etiology. Thirty-one patients with a clinical diagnosis of one of the RASopathy syndromes were included in the study. Of these, 26 (83.8%) had a clinical diagnosis of Noonan syndrome, whereas 5 had a clinical diagnosis of either Costello, LEOPARD or cardio-facio-cutaneous syndromes. Twenty of 31 (64.5%) patients were found to be mutation positive. Mutations in PTPN11, SOS1 and SHOC2 genes were detected in patients with Noonan syndrome (57.6%). Mutations in MEK1, PTPN11, BRAF and HRAS genes were detected in the remaining. Pulmonary stenosis was the most common (61.5%) cardiac anomaly. Among Noonan syndrome patients with a confirmed mutation, mild intellectual disability tended to be more common in patients with PTPN11 mutation than in those with SOS1 mutation. Hematologic evaluation revealed coagulation defects in three Noonan syndrome patients with a mutation. This is currently the largest clinical and molecular study in Turkish RASopathy patients. Our findings indicate that molecular epidemiology and genotype-phenotype correlations in RASopathies are relatively independent from the ethnic population background.
authors.affiliation: Pediatric Genetics Unit, Department of Pediatrics, Faculty of Medicine, Hacettepe University, Ankara, Turkey. pelinozlem@hacettepe.edu.tr
authors.forename: P Ö
authors.initials: PÖ
authors.lastname: Şimşek-Kiper
authors.forename: Y
authors.initials: Y
authors.lastname: Alanay
authors.forename: B
authors.initials: B
authors.lastname: Gülhan
authors.forename: C
authors.initials: C
authors.lastname: Lissewski
authors.forename: D
authors.initials: D
authors.lastname: Türkyilmaz
authors.forename: D
authors.initials: D
authors.lastname: Alehan
authors.forename: M
authors.initials: M
authors.lastname: Cetin
authors.forename: G E
authors.initials: GE
authors.lastname: Utine
authors.forename: M
authors.initials: M
authors.lastname: Zenker
authors.forename: K
authors.initials: K
authors.lastname: Boduroğlu
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D056685:Costello Syndrome / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D004252:DNA Mutational Analysis; D004476:Ectodermal Dysplasia / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D019066:Facies; D005183:Failure to Thrive / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D056726:Genetic Association Studies; D006330:Heart Defects, Congenital / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D044542:LEOPARD Syndrome / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D048369:MAP Kinase Kinase 1 / Q000235:genetics; D009154:Mutation; D009634:Noonan Syndrome / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D010641:Phenotype; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D020837:SOS1 Protein / Q000235:genetics; D014421:Turkey; D018631:ras Proteins / Q000235:genetics*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C112913:SHOC2 protein, human; D020837:SOS1 Protein; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins