Severe growth hormone insensitivity resulting from total absence of signal transducer and activator of transcription 5b

Vivian Hwa, Brian Little, Pelin Adiyaman, Eric M. Kofoed, Katherine L. Pratt, Gonul Ocal, Merih Berberoglu, Ronald (Ron) Rosenfeld

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4260-4266
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume90
Issue number7
DOIs
StatePublished - Jul 2005

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STAT5 Transcription Factor
Insulin-Like Growth Factor I
Growth Hormone
Laron Syndrome
Growth
STAT Transcription Factors
Insulin-Like Growth Factor Binding Protein 3
Fibroblasts
Pedigree
Serum
DNA Sequence Analysis
Cell culture
Gene expression
Exons
Proteins
Nucleotides
Genes
Gene Expression
Skin
Mutation

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Severe growth hormone insensitivity resulting from total absence of signal transducer and activator of transcription 5b. / Hwa, Vivian; Little, Brian; Adiyaman, Pelin; Kofoed, Eric M.; Pratt, Katherine L.; Ocal, Gonul; Berberoglu, Merih; Rosenfeld, Ronald (Ron).

In: Journal of Clinical Endocrinology and Metabolism, Vol. 90, No. 7, 07.2005, p. 4260-4266.

Research output: Contribution to journalArticle

Hwa, V, Little, B, Adiyaman, P, Kofoed, EM, Pratt, KL, Ocal, G, Berberoglu, M & Rosenfeld, RR 2005, 'Severe growth hormone insensitivity resulting from total absence of signal transducer and activator of transcription 5b', Journal of Clinical Endocrinology and Metabolism, vol. 90, no. 7, pp. 4260-4266. https://doi.org/10.1210/jc.2005-0515
Hwa, Vivian ; Little, Brian ; Adiyaman, Pelin ; Kofoed, Eric M. ; Pratt, Katherine L. ; Ocal, Gonul ; Berberoglu, Merih ; Rosenfeld, Ronald (Ron). / Severe growth hormone insensitivity resulting from total absence of signal transducer and activator of transcription 5b. In: Journal of Clinical Endocrinology and Metabolism. 2005 ; Vol. 90, No. 7. pp. 4260-4266.
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AU - Little, Brian

AU - Adiyaman, Pelin

AU - Kofoed, Eric M.

AU - Pratt, Katherine L.

AU - Ocal, Gonul

AU - Berberoglu, Merih

AU - Rosenfeld, Ronald (Ron)

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