title: Exclusion of PTPN11 mutations in Costello syndrome: further evidence for distinct genetic etiologies for Noonan, cardio-facio-cutaneous and Costello syndromes.
abstract: Costello syndrome (CS) is a rare, multiple congenital anomaly syndrome with characteristic dysmorphic features, cardiac anomalies and a tendency to develop certain cancers. Phenotypically there is some overlap with other genetic disorders, notably cardio-facio-cutaneous (CFC) syndrome and Noonan syndrome (NS), suggesting that these syndromes may be allelic. We recently identified PTPN11, which encodes the non-receptor protein tyrosine phosphatase, SHP-2, as a major NS disease gene. In this report, we screened a cohort of 27 patients, with the clinical diagnosis of CS, for PTPN11 mutations using denaturing high performance liquid chromatography analysis. No mutations of the PTPN11 gene were found in the CS patients. Common polymorphisms in introns 6 and 7 and exon 8 were identified in four individuals. With our previous exclusion of PTPN11 mutations in CFC syndrome, these data suggest distinct genetic etiologies for Noonan, CFC and Costello syndromes.
authors.affiliation: Department of Pediatrics, Mount Sinai School of Medicine, New York, New York, USA.
authors.forename: M
authors.initials: M
authors.lastname: Tartaglia
authors.forename: P D
authors.initials: PD
authors.lastname: Cotter
authors.forename: G
authors.initials: G
authors.lastname: Zampino
authors.forename: B D
authors.initials: BD
authors.lastname: Gelb
authors.forename: K A
authors.initials: KA
authors.lastname: Rauen
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D000483:Alleles; D002851:Chromatography, High Pressure Liquid; D015331:Cohort Studies; D005091:Exons; D006130:Growth Disorders / Q000235:genetics; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D007438:Introns; D007621:Karyotyping; D009154:Mutation; D009634:Noonan Syndrome / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D012868:Skin Abnormalities / Q000235:genetics; D013577:Syndrome
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases