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J Clin Endocrinol Metab. 2005 Sep;90(9):5156-60. Epub 2005 Jun 14.

PTPN11 (protein tyrosine phosphatase, nonreceptor type 11) mutations and response to growth hormone therapy in children with Noonan syndrome.

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  • 1Hospital das Clinicas, Labaratorio de Hormonios, Avenue Dr. Eneas de Carvalho Aguiar 155 PAMB, 2 Andar Bloco 6, 05403-900 Sao Paulo, Brazil.



The cause of growth impairment in Noonan syndrome (NS) remains unclear. Mutations in PTPN11 (protein tyrosine phosphatase, nonreceptor type 11) that codify constitutively activated Src homology protein tyrosine phosphatase-2 tyrosine phosphatase and may interfere with GH and IGF-I signaling were identified in approximately 40% of patients with NS.


The objective of this study was to evaluate the influence of PTPN11 status on response to human GH (hGH) treatment in NS children with short stature.


This study was performed at a university hospital.


The study design was to conduct a retrospective analysis of 3 yr of hGH treatment and genotyping of PTPN11 in patients with NS.


Fourteen NS patients, half of them with PTPN11 mutations in heterozygous state, were studied. At the beginning of treatment, there were no clinical or laboratory differences between groups with and without mutations in the PTPN11 gene.


Patients were treated with hGH (47 microg/kg.d).


The main outcome measures were PTPN11 genotype, change in IGF-I levels, and change in height sd score.


Patients with mutations in PTPN11 presented a significantly smaller increment in IGF-I levels during the treatment compared with patients without mutations (86 +/- 67 and 202 +/- 93 microg/liter, respectively; P = 0.03). hGH treatment significantly improved growth velocity in both groups, with slightly better results observed in patients without mutations. This was translated into greater gains in height sd score relation to baseline during the 3 yr of treatment in patients without mutations (+1.7 +/- 0.1) compared with those with mutations (+0.8 +/- 0.4; P < 0.01).


Our findings suggest that the presence of PTPN11 mutations in patients with NS indicates a reduced growth response to long-term hGH treatment.

[PubMed - indexed for MEDLINE]
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