TY - JOUR
T1 - Severe growth hormone insensitivity resulting from total absence of signal transducer and activator of transcription 5b
AU - Hwa, Vivian
AU - Little, Brian
AU - Adiyaman, Pelin
AU - Kofoed, Eric M.
AU - Pratt, Katherine L.
AU - Ocal, Gonul
AU - Berberoglu, Merih
AU - Rosenfeld, Ron G.
PY - 2005/7
Y1 - 2005/7
N2 - Context: The central clinical feature of GH insensitivity (GHI) is severe growth failure associated with elevated serum concentrations of GH and abnormally low serum levels of IGF-I. GHI can be the result of an abnormality in the GH receptor or aberrancies downstream of the GH receptor. Objective: We investigated the GH-IGF-I axis in a young female GHI subject who presented with a height of 114 cm (-7.8 SD score) at age 16.4 yr. Patient: The subject, from a consanguineous pedigree, had circulating levels of GH and GH-binding protein that were normal to elevated, whereas IGF-I (7.2 ng/ml; normal, 242-600), IGF-binding protein-3 (543 ng/ml; normal, 2500-4800), and acid-labile subunit (1.22 μg/ml; normal, 5.6-16) levels were abnormally low and failed to increase during an IGF-I generation test. Design: Dermal fibroblast cultures were established with the consent of the patient and family. Immunoblot analysis of cell lysates and DNA sequencing of her signal transducer and activator of transcription 5b (STAT5b), a critical intermediate of the GH-IGF-I axis, were performed. Results: Sequencing of the STAT5b gene revealed a novel homozygous insertion of a single nucleotide in exon 10. The insertion resulted in a frame shift, leading to early protein termination and consequent lack of immunodetectable STAT5b protein. Conclusion: The identification of a second case of severe growth failure associated with STAT5b mutation implicates a unique and critical role for STAT5b in GH stimulation of IGF-I gene expression and statural growth.
AB - Context: The central clinical feature of GH insensitivity (GHI) is severe growth failure associated with elevated serum concentrations of GH and abnormally low serum levels of IGF-I. GHI can be the result of an abnormality in the GH receptor or aberrancies downstream of the GH receptor. Objective: We investigated the GH-IGF-I axis in a young female GHI subject who presented with a height of 114 cm (-7.8 SD score) at age 16.4 yr. Patient: The subject, from a consanguineous pedigree, had circulating levels of GH and GH-binding protein that were normal to elevated, whereas IGF-I (7.2 ng/ml; normal, 242-600), IGF-binding protein-3 (543 ng/ml; normal, 2500-4800), and acid-labile subunit (1.22 μg/ml; normal, 5.6-16) levels were abnormally low and failed to increase during an IGF-I generation test. Design: Dermal fibroblast cultures were established with the consent of the patient and family. Immunoblot analysis of cell lysates and DNA sequencing of her signal transducer and activator of transcription 5b (STAT5b), a critical intermediate of the GH-IGF-I axis, were performed. Results: Sequencing of the STAT5b gene revealed a novel homozygous insertion of a single nucleotide in exon 10. The insertion resulted in a frame shift, leading to early protein termination and consequent lack of immunodetectable STAT5b protein. Conclusion: The identification of a second case of severe growth failure associated with STAT5b mutation implicates a unique and critical role for STAT5b in GH stimulation of IGF-I gene expression and statural growth.
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U2 - 10.1210/jc.2005-0515
DO - 10.1210/jc.2005-0515
M3 - Article
C2 - 15827093
AN - SCOPUS:23044470651
SN - 0021-972X
VL - 90
SP - 4260
EP - 4266
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 7
ER -