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

Autor(es)

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]}

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: EUROPEAN JOURNAL OF ENDOCRINOLOGY; v. 163, n. 2, p. 349-355, AUG 2010.
• Citações Web of Science: 29

Resumo

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)

• Processo FAPESP: 09/00313-3 - Pesquisa de mutações no gene do receptor do secretagogo de hormônio de crescimento (GHSR) em crianças com baixa estatura idiopática e deficiência isolada de hormônio de crescimento
• Beneficiário: Alexander Augusto de Lima Jorge
• Linha de fomento: Auxílio à Pesquisa - Regular