title: Mutation Spectrum and Phenotypic Features in Noonan Syndrome with PTPN11 Mutations: Definition of Two Novel Mutations.
abstract: OBJECTIVE
  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.
authors.affiliation: Division of Genetics, Department of Pediatrics, School of Medicine, Ege University, 35100, Bornova, Izmir, Turkey. tahiratik@yahoo.com.
authors.forename: Tahir
authors.initials: T
authors.lastname: Atik
authors.affiliation: Department of Medical Genetics, School of Medicine, Ege University, Izmir, Turkey.
authors.forename: Ayca
authors.initials: A
authors.lastname: Aykut
authors.affiliation: Department of Medical Genetics, Dr. Behcet Uz Children's Hospital, Izmir, Turkey.
authors.forename: Filiz
authors.initials: F
authors.lastname: Hazan
authors.affiliation: Department of Medical Genetics, School of Medicine, Ege University, Izmir, Turkey.
authors.forename: Huseyin
authors.initials: H
authors.lastname: Onay
authors.affiliation: Division of Endocrinology, Department of Pediatrics, School of Medicine, Ege University, Izmir, Turkey.
authors.forename: Damla
authors.initials: D
authors.lastname: Goksen
authors.affiliation: Division of Endocrinology, Department of Pediatrics, School of Medicine, Ege University, Izmir, Turkey.
authors.forename: Sukran
authors.initials: S
authors.lastname: Darcan
authors.affiliation: Department of Genetics, School of Medicine, Ankara University, Ankara, Turkey.
authors.forename: Ajlan
authors.initials: A
authors.lastname: Tukun
authors.affiliation: Division of Genetics, Department of Pediatrics, School of Medicine, Ege University, 35100, Bornova, Izmir, Turkey.|Department of Medical Genetics, School of Medicine, Ege University, Izmir, Turkey.
authors.forename: Ferda
authors.initials: F
authors.lastname: Ozkinay
mesh_terms: D002648:Child; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D009634:Noonan Syndrome / Q000235:genetics*; D010641:Phenotype; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics*
chemical_list: C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11
keywords: Noonan syndrome; PTPN11; Pulmonary stenosis; Rasopathy; Short stature
references.citation: Am J Med Genet. 1994 Nov 1;53(2):187-91
references.pmid: 7856646
references.citation: Orphanet J Rare Dis. 2007 Jan 14;2:4
references.pmid: 17222357
references.citation: J Med Genet. 2008 Dec;45(12):832
references.pmid: 19047498
references.citation: Am J Hum Genet. 2004 Sep;75(3):492-7
references.pmid: 15248152
references.citation: Genet Test. 2006 Fall;10(3):186-91
references.pmid: 17020470
references.citation: Pediatrics. 2010 Oct;126(4):746-59
references.pmid: 20876176
references.citation: Am J Hum Genet. 2002 Jun;70(6):1555-63
references.pmid: 11992261
references.citation: J Formos Med Assoc. 2013 Nov;112(11):707-12
references.pmid: 24183200
references.citation: Nat Methods. 2010 Aug;7(8):575-6
references.pmid: 20676075
references.citation: J Pediatr. 2004 Mar;144(3):368-74
references.pmid: 15001945
references.citation: Nat Genet. 2001 Dec;29(4):465-8
references.pmid: 11704759
references.citation: Nat Methods. 2010 Apr;7(4):248-9
references.pmid: 20354512
references.citation: Am J Med Genet A. 2005 Apr 15;134A(2):165-70
references.pmid: 15723289
references.citation: Horm Res. 2009;71(4):185-93
references.pmid: 19258709
references.citation: Horm Res. 2004;62 Suppl 3:56-9
references.pmid: 15539800
references.citation: Am J Med Genet. 1981;10(1):37-50
references.pmid: 7294061
references.citation: Eur J Pediatr. 2012 Jan;171(1):51-8
references.pmid: 21590266
references.citation: Eur J Hum Genet. 2003 Feb;11(2):201-6
references.pmid: 12634870
references.citation: Am J Med Genet. 1985 Jul;21(3):493-506
references.pmid: 3895929
references.citation: Clin Genet. 2013 Feb;83(2):181-6
references.pmid: 22420426