title: Protein-tyrosine phosphatase, nonreceptor type 11 mutation analysis and clinical assessment in 45 patients with Noonan syndrome.
abstract: We report on PTPN11 (protein-tyrosine phosphatase, nonreceptor type 11) mutation analysis and clinical assessment in 45 patients with Noonan syndrome. Sequence analysis was performed for all of the coding exons 1-15 of PTPN11, revealing a novel 3-bp deletion mutation and 10 recurrent missense mutations in 18 patients. Clinical assessment showed that 1) the growth pattern was similar in mutation-positive and mutation-negative patients, with no significant difference in birth length [-0.6 +/- 2.2 sd (n = 10) vs. -0.6 +/- 1.4 sd (n = 21); P = 0.95], childhood height [-2.6 +/- 1.1 sd (n = 14) vs. -2.1 +/- 1.6 sd (n = 23); P = 0.28], or target height [-0.4 +/- 0.9 sd (n = 14) vs. -0.2 +/- 0.7 sd (n = 17); P = 0.52]; 2) pulmonary valve stenosis was more frequent in mutation-positive patients than in mutation-negative patients (10 of 18 vs. 6 of 27; P = 0.02), as was atrial septal defect (10 of 18 vs. 4 of 27; P = 0.005), whereas hypertrophic cardiomyopathy was present in five mutation-negative patients only; and 3) other features were grossly similar in the prevalence between mutation-positive and mutation-negative patients, but hematological abnormalities, such as bleeding diathesis and juvenile myelomonocytic leukemia, were exclusively present in mutation-positive patients (5 of 18 vs. 0 of 27; P = 0.007). The results suggest that PTPN11 mutations account for approximately 40% of Noonan syndrome patients, as has been reported previously. Furthermore, assessment of clinical features, in conjunction with data reported previously, implies that the type of cardiovascular lesions and the occurrence of hematological abnormalities are different in mutation-positive and mutation-negative patients, whereas the remaining findings are similar in the two groups of patients.
authors.affiliation: Department of Pediatrics, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Yoshida
authors.forename: Tomonobu
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Toshiro
authors.initials: T
authors.lastname: Nagai
authors.forename: Eiichi
authors.initials: E
authors.lastname: Kinoshita
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kanegane
authors.forename: Kenji
authors.initials: K
authors.lastname: Ohyama
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Onishi
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Hanew
authors.forename: Torayuki
authors.initials: T
authors.lastname: Okuyama
authors.forename: Reiko
authors.initials: R
authors.lastname: Horikawa
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ogata
mesh_terms: D000293:Adolescent; D000328:Adult; D001827:Body Height; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D017353:Gene Deletion; D006128:Growth; D006402:Hematologic Diseases / Q000235:genetics; D006801:Humans; D015994:Incidence; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D009634:Noonan Syndrome / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D011666:Pulmonary Valve Stenosis / Q000453:epidemiology / 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