title: Genotypic and phenotypic characterization of Noonan syndrome: new data and review of the literature.
abstract: Noonan syndrome (NS) is an autosomal dominant disorder, characterized by short stature, minor facial anomalies, and congenital heart defects. In approximately 50% of cases the condition is caused by missense mutations in the PTPN11 gene on chromosome 12, resulting in a gain of function of the protein SHP-2. In this study, PTPN11 mutation analysis was performed in 170 NS patients. In 76 (45%) of them a mutation was identified. We report on the distribution of these mutations, as well as on genotype-phenotype relationships. The benefit of the NS scoring system developed by van der Burgt et al. [(1994); Am J Med Genet 53:187-191] is shown, among physicians who consequently based their diagnosis on the NS scoring system the percentage mutation positive subjects was 54%, whereas this percentage was only 39% among physicians who made less use of the scoring system. In two patients with some uncommon manifestations mutations were found in the C-SH2 domain, a region in which defects are not often identified in NS. A trend was observed in patients carrying the 922A --> G change (Asn308Asp) receiving normal education. In one patient with NS and mild juvenile myelomonocytic leukemia (JMML) the mutation 218C --> T (Thr73Ile) was found. This confirms previous findings indicating that individuals with NS with specific mutations in PTPN11 are at risk of developing JMML.
authors.affiliation: Department of Human Genetics, Radboud University Nijmegen Medical Centre, The Netherlands.
authors.forename: Marjolijn
authors.initials: M
authors.lastname: Jongmans
authors.forename: Erik A
authors.initials: EA
authors.lastname: Sistermans
authors.forename: Alwin
authors.initials: A
authors.lastname: Rikken
authors.forename: Willy M
authors.initials: WM
authors.lastname: Nillesen
authors.forename: Rienk
authors.initials: R
authors.lastname: Tamminga
authors.forename: Michael
authors.initials: M
authors.lastname: Patton
authors.forename: Esther M
authors.initials: EM
authors.lastname: Maier
authors.forename: Marco
authors.initials: M
authors.lastname: Tartaglia
authors.forename: Kees
authors.initials: K
authors.lastname: Noordam
authors.forename: Ineke
authors.initials: I
authors.lastname: van der Burgt
mesh_terms: D000328:Adult; D002648:Child; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009154:Mutation; D009634:Noonan Syndrome / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D012196:Review Literature as Topic; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D018909:src Homology Domains / Q000235:genetics
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases