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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

A novel STAT5B mutation causing GH insensitivity syndrome associated with hyperprolactinemia and immune dysfunction in two male siblings

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Pugliese-Pires, Patricia N. [1] ; Tonelli, Carlos A. [2] ; Dora, Jose M. [3, 4, 5] ; Silva, Paulo C. A. [6] ; Czepielewski, Mauro [7] ; Simoni, Genoir [6] ; Arnhold, Ivo J. P. [1] ; Jorge, Alexander A. L. [1, 8]
Total Authors: 8
[1] Univ Sao Paulo, Disciplina Endocrinol, Unidade Endocrinol Desenvolvimento, Hosp Clin, Lab Hormonios & Genet Mol LIM 42, Fac Me, BR-05403900 Sao Paulo - Brazil
[2] Univ Extremo Santa Catarina UNESC, Fac Med, BR-88806000 Criciuma - Brazil
[3] Hosp Clin Porto Alegre, Serv Patol Clin, BR-90035000 Rio Grande Do Sul - Brazil
[4] Hosp Clin Porto Alegre, Serv Endocrinol, BR-90035000 Rio Grande Do Sul - Brazil
[5] Univ Fed Rio Grande do Sul, Fac Med, BR-90035000 Rio Grande Do Sul - Brazil
[6] Hosp Infantil Joana de Gusmao, Unidade Endocrinol Pediat, BR-88025301 Florianopolis, SC - Brazil
[7] Univ Fed Rio Grande do Sul, Serv Endocrinol, Hosp Clin Porto Alegre, Fac Med, BR-90035000 Rio Grande Do Sul - Brazil
[8] Univ Sao Paulo, Fac Med, Unidade Endocrinol Genet LIM 25, Disciplina Endocrinol, BR-01246903 Sao Paulo - Brazil
Total Affiliations: 8
Document type: Journal article
Source: EUROPEAN JOURNAL OF ENDOCRINOLOGY; v. 163, n. 2, p. 349-355, AUG 2010.
Web of Science Citations: 29

Background: GH insensitivity (GHI) syndrome caused by STAT5B mutations was recently reported, and it is characterized by extreme short stature and immune dysfunction. Treatment with recombinant human IGF1 (rhIGF1) is approved for patients with GHI, but the growth response to this therapy in patients with STAT5B mutations has not been reported. Objectives: To report the clinical features, molecular findings, and the short-term growth response to rhIGF1 therapy in patients with STAT5B mutation. Subjects and methods: Hormonal and immunological evaluations were performed in two male siblings with GHI associated with atopic eczema, interstitial lung disease, and thrombocytopenic purpura. STAT5B genes were directly sequenced. The younger sibling was treated with rhIGF1 at a dose of 110 mu g/kg BID. Results: Both siblings had laboratory findings compatible with GHI associated with hyperprolactinemia. Lymphopenia and reduced number of natural killer cells without immunoglobulin abnormalities were observed. STAT5B sequence revealed a homozygous frameshift mutation (p.L142fsX161) in both siblings. The younger sibling (9.9 years of age) was treated with rhIGF1 at appropriate dosage, and he did not present any significant change in his growth velocity (from 2.3 to 3.0 cm/year after 1.5 years of therapy). The presence of a chronic illness could possibly be responsible for the poor result of rhIGF1 treatment. Further studies in patients with STAT5B defects are necessary to define the response to rhIGF1 treatment in this disorder. Conclusion: GHI associated with immune dysfunction, especially interstitial lung disease, and hyperprolactinemia is strongly suggestive of a mutation in STAT5B in both sexes. (AU)

FAPESP's process: 09/00313-3 - Study of growth hormone secretagogue receptor (GHSR) gene in children with isolated growth hormone deficiency and children with idiopatic short stature
Grantee:Alexander Augusto de Lima Jorge
Support type: Regular Research Grants