title: Spectrum of mutations in PTPN11 and genotype-phenotype correlation in 96 patients with Noonan syndrome and five patients with cardio-facio-cutaneous syndrome.
abstract: Noonan syndrome (NS) is a relatively common, but genetically heterogeneous autosomal dominant malformation syndrome. Characteristic features are proportionate short stature, dysmorphic face, and congenital heart defects. Only recently, a gene involved in NS could be identified. It encodes the non-receptor protein tyrosine phosphatase SHP-2, which is an important molecule in several intracellular signal transduction pathways that control diverse developmental processes, most importantly cardiac semilunar valvulogenesis. We have screened this gene for mutations in 96 familial and sporadic, well-characterised NS patients and identified 15 different missense mutations in a total of 32 patients (33%), including 23 index patients. Most changes clustered in one exon which encodes parts of the N-SH2 domain. Five of the mutations were recurrent. Interestingly, no mutations in the PTPN11 gene were detected in five additional patients with cardio-facio-cutaneous (CFC) syndrome, which shows clinical similarities to NS.
authors.affiliation: Max-Planck-Institute for Molecular Genetics, Berlin, Germany.
authors.forename: Luciana
authors.initials: L
authors.lastname: Musante
authors.forename: Hans G
authors.initials: HG
authors.lastname: Kehl
authors.forename: Frank
authors.initials: F
authors.lastname: Majewski
authors.forename: Peter
authors.initials: P
authors.lastname: Meinecke
authors.forename: Susann
authors.initials: S
authors.lastname: Schweiger
authors.forename: Gabriele
authors.initials: G
authors.lastname: Gillessen-Kaesbach
authors.forename: Dagmar
authors.initials: D
authors.lastname: Wieczorek
authors.forename: Georg K
authors.initials: GK
authors.lastname: Hinkel
authors.forename: Sigrid
authors.initials: S
authors.lastname: Tinschert
authors.forename: Maria
authors.initials: M
authors.lastname: Hoeltzenbein
authors.forename: Hans-Hilger
authors.initials: HH
authors.lastname: Ropers
authors.forename: Vera M
authors.initials: VM
authors.lastname: Kalscheuer
mesh_terms: D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009634:Noonan Syndrome / Q000235:genetics*; D010641:Phenotype; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases