Tahir Atik1, Ayca Aykut2, Filiz Hazan3, Huseyin Onay2, Damla Goksen4, Sukran Darcan4, Ajlan Tukun5, Ferda Ozkinay6,2. 1. Division of Genetics, Department of Pediatrics, School of Medicine, Ege University, 35100, Bornova, Izmir, Turkey. tahiratik@yahoo.com. 2. Department of Medical Genetics, School of Medicine, Ege University, Izmir, Turkey. 3. Department of Medical Genetics, Dr. Behcet Uz Children's Hospital, Izmir, Turkey. 4. Division of Endocrinology, Department of Pediatrics, School of Medicine, Ege University, Izmir, Turkey. 5. Department of Genetics, School of Medicine, Ankara University, Ankara, Turkey. 6. Division of Genetics, Department of Pediatrics, School of Medicine, Ege University, 35100, Bornova, Izmir, Turkey.
Abstract
OBJECTIVES: To evaluate the spectrum of PTPN11 gene mutations in Noonan syndrome patients and to study the genotype-phenotype associations. METHODS: In this study, twenty Noonan syndrome patients with PTPN11 mutations were included. The patients underwent a detailed clinical and physical evaluation. To identify inherited cases, parents of all mutation positive patients were analyzed. RESULTS: Thirteen different PTPN11 mutations, two of them being novel, were detected in the study group. These mutations included eleven missense mutations: p.G60A, p.D61N, p.Y62D, p.Y63C, p.E69Q, p.Q79R, p.Y279C,p.N308D, p.N308S, p.M504V, p.Q510R and two novel missense mutations: p.I56V and p.I282M. The frequency of cardiac abnormalities and short stature were found to be 80 % and 80 %, respectively. Mental retardation was not observed in patients having exon 8 mutations. No significant correlations were detected between other phenotypic features and genotypes. CONCLUSIONS: By identifying genotype-phenotype correlations, this study provides information on phenotypes observed in NS patients with different PTPN11 mutations.
OBJECTIVES: To evaluate the spectrum of PTPN11 gene mutations in Noonan syndromepatients and to study the genotype-phenotype associations. METHODS: In this study, twenty Noonan syndromepatients with PTPN11 mutations were included. The patients underwent a detailed clinical and physical evaluation. To identify inherited cases, parents of all mutation positive patients were analyzed. RESULTS: Thirteen different PTPN11 mutations, two of them being novel, were detected in the study group. These mutations included eleven missense mutations: p.G60A, p.D61N, p.Y62D, p.Y63C, p.E69Q, p.Q79R, p.Y279C,p.N308D, p.N308S, p.M504V, p.Q510R and two novel missense mutations: p.I56V and p.I282M. The frequency of cardiac abnormalities and short stature were found to be 80 % and 80 %, respectively. Mental retardation was not observed in patients having exon 8 mutations. No significant correlations were detected between other phenotypic features and genotypes. CONCLUSIONS: By identifying genotype-phenotype correlations, this study provides information on phenotypes observed in NSpatients with different PTPN11 mutations.
Entities:
Keywords:
Noonan syndrome; PTPN11; Pulmonary stenosis; Rasopathy; Short stature
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