Clin Genet 2013: 83: 181 – 186 Printed in Singapore. All rights reserved  2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd CLINICAL GENETICS doi: 10.1111/j.1399-0004.2012.01875.x Short Report Clinical and molecular analysis of RASopathies in a group of Turkish patients S ¸ ims ¸ek-Kiper P ¨ O, Alanay Y, G¨ ulhan B, Lissewski C, T¨ urkyılmaz D, Alehan D, C ¸ etin M, Utine GE, Zenker M, Boduro˘ glu K. Clinical and molecular analysis of patients with RASopathies in Turkish patients. Clin Genet 2013: 83: 181–186.  John Wiley & Sons A/S. Published by Blackwell Publishing Ltd, 2012 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. Conflict of interest The authors declare that they have no conflict of interest. P ¨ OS ¸ ims ¸ ek-Kiper a , Y Alanay b , BG¨ ulhan a , C Lissewski c , DT¨ urkyılmaz d , D Alehan e , MC ¸ etin f , GE Utine a , M Zenker c and K Boduro ˘ glu a a Pediatric Genetics Unit, Department of Pediatrics, Faculty of Medicine, Hacettepe University, Ankara, Turkey, b Pediatric Genetics Unit, Department of Pediatrics, Faculty of Medicine, Acibadem University, Istanbul, Turkey, c Institute of Human Genetics, University Hospital Magdeburg, Magdeburg, Germany, d Audiology Unit, Department of Ear-Nose-Throat, Faculty of Medicine, Hacettepe University, Ankara, Turkey, e Pediatric Cardiology Unit, Department of Pediatrics, Faculty of Medicine, Hacettepe University, Ankara, Turkey, and f Pediatric Hematology Unit, Department of Pediatrics, Faculty of Medicine, Hacettepe University, Ankara, Turkey Key words: BRAF – cardio- facio-cutaneous – Costello – HRAS – LEOPARD – Noonan – PTPN11 – SHOC2 – SOS1 Corresponding author: Pelin ¨ Ozlem S ¸ ims ¸ ek-Kiper, MD, Pediatric Genetics Unit, Hacettepe University ˙ Ihsan Do ˘ gramacı Children’s Hospital, 06100 Sihhiye, Ankara, Turkey. Tel.:: +90 312 311 55 22; fax: +90 312 311 55 22; e-mail: pelinozlem@hacettepe.edu.tr Received 11 December 2011, revised and accepted for publication 12 March 2012 Recent genetic studies have showed that Noonan syn- drome (NS) and related disorders (now collectively called ‘RASopathies’) are caused by germline muta- tions in a number of genes interacting in the same Ras/mitogen-activated protein kinase pathway (1–3). The overlapping clinical features, wide spectrum of phenotypic expression within each trait, and the absence of clinical features with pathognomonic value and consensus on diagnostic criteria can make diagnosis of NS and related disorders challenging (4). There- fore, molecular analysis has become an important key for the verification of clinical diagnosis and estab- lishment of individual follow-up plans. The most consistent genotype–phenotype correlations that have 181