Clinical and molecular analysis of RASopathies in a group of Turkish patients

• Published in: Clinical genetics 2013-02, Vol.83 (2), p.181-186
• Main Authors: Şimşek-Kiper, PÖ, Alanay, Y, Gülhan, B, Lissewski, C, Türkyılmaz, D, Alehan, D, Çetin, M, Utine, GE, Zenker, M, Boduroğlu, K
• Format: Article
• Language: English
• Subjects: Abnormalities, Multiple - diagnosis; Abnormalities, Multiple - genetics; Abnormalities, Multiple - pathology; Biological and medical sciences; BRAF; cardio-facio-cutaneous; Clinical trials; Coagulation; Costello; Costello Syndrome - diagnosis; Costello Syndrome - genetics; Costello Syndrome - pathology; DNA Mutational Analysis; Ectodermal Dysplasia - diagnosis; Ectodermal Dysplasia - genetics; Ectodermal Dysplasia - pathology; Epidemiology; Etiology; Facies; Failure to Thrive - diagnosis; Failure to Thrive - genetics; Failure to Thrive - pathology; Fundamental and applied biological sciences. Psychology; Genetic Association Studies; Genetics of eukaryotes. Biological and molecular evolution; Heart; Heart Defects, Congenital - diagnosis; Heart Defects, Congenital - genetics; Heart Defects, Congenital - pathology; HRAS; Humans; Intellectual Disability - genetics; Intracellular Signaling Peptides and Proteins - genetics; LEOPARD; LEOPARD Syndrome - diagnosis; LEOPARD Syndrome - genetics; LEOPARD Syndrome - pathology; Lung; MAP Kinase Kinase 1 - genetics; Medical genetics; Medical sciences; Mental retardation; Minority & ethnic groups; Molecular and cellular biology; Molecular biology; Mutation; Noonan; Noonan Syndrome - diagnosis; Noonan Syndrome - genetics; Noonan Syndrome - pathology; Patients; Phenotype; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Proto-Oncogene Proteins B-raf - genetics; Proto-Oncogene Proteins p21(ras) - genetics; PTPN11; ras Proteins - genetics; SHOC2; SOS1; SOS1 Protein - genetics; Stenosis; Turkey
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/j.1399-0004.2012.01875.x

Şimşek‐Kiper PÖ, Alanay Y, Gülhan B, Lissewski C, Türkyılmaz D, Alehan D, Çetin M, Utine GE, Zenker M, Boduroğlu K. Clinical and molecular analysis of patients with RASopathies in Turkish patients. 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.