Protein-tyrosine phosphatase, nonreceptor type 11 mutation analysis and clinical assessment in 45 patients with Noonan syndrome

Rie Yoshida, Tomonobu Hasegawa, Yukihiro Hasegawa, Toshiro Nagai, Eiichi Kinoshita, Yoko Tanaka, Hirokazu Kanegane, Kenji Ohyama, Toshikazu Onishi, Kunihiko Hanew, Torayuki Okuyama, Reiko Horikawa, Toshiaki Tanaka, Tsutomu Ogata

Research output: Contribution to journalArticle

83 Citations (Scopus)

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 esons 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.

Original languageEnglish
Pages (from-to)3359-3364
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume89
Issue number7
DOIs
Publication statusPublished - 2004 Jul 1

    Fingerprint

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Yoshida, R., Hasegawa, T., Hasegawa, Y., Nagai, T., Kinoshita, E., Tanaka, Y., Kanegane, H., Ohyama, K., Onishi, T., Hanew, K., Okuyama, T., Horikawa, R., Tanaka, T., & Ogata, T. (2004). Protein-tyrosine phosphatase, nonreceptor type 11 mutation analysis and clinical assessment in 45 patients with Noonan syndrome. Journal of Clinical Endocrinology and Metabolism, 89(7), 3359-3364. https://doi.org/10.1210/jc.2003-032091