Extreme elevation of serum growth hormone-binding protein concentrations resulting from a novel heterozygous splice site mutation of the growth hormone receptor gene
| Autor: | Brian M. Little, Katherine L. Pratt, Ron G. Rosenfeld, Daisy Chin, Vivian Hwa, Anna M. Aalbers, Stuart J. Frank |
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| Rok vydání: | 2008 |
| Předmět: |
Male
medicine.medical_specialty Heterozygote Endocrinology Diabetes and Metabolism RNA Splicing Growth hormone receptor Biology medicine.disease_cause Exon Endocrinology Growth hormone-binding protein Internal medicine medicine Humans Insulin-Like Growth Factor I Receptor Child Mutation Splice site mutation Base Sequence Human Growth Hormone Intron Receptors Somatotropin Molecular biology Blot Insulin-Like Growth Factor Binding Proteins Insulin-Like Growth Factor Binding Protein 3 Pediatrics Perinatology and Child Health RNA Splice Sites Carrier Proteins hormones hormone substitutes and hormone antagonists |
| Zdroj: | Hormone research. 71(5) |
| ISSN: | 1423-0046 |
| Popis: | Background/Aims: Circulating growth hormone-binding protein (GHBP), in humans, is the proteolytic product of the growth hormone receptor (GHR). We investigated a prepubertal male subject who was of short stature, but who had a markedly elevated serum level of GHBP. Methods: Serum and DNA from the patient and his mother were analyzed. Results: Both the patient and mother had serum GHBP concentrations over 100-fold higher than normal, by assays, and Western and ligand blot analysis. Sequencing of the GHR gene revealed a novel heterozygous C>A transversion at position 785-3 in the acceptor splice site of intron 7. Conclusion: In silico analysis of the altered sequence suggested that 785-3(C>A) is a splicing mutation, with either retention of intron 7 or the skipping of exon 8. The consequence is a truncated GHR lacking the transmembrane domain (encoded by exon 8) and the cytoplasmic domain. We hypothesize that this GHR variant cannot anchor to the cell membrane, and the continual secretion into the circulation explains the elevated levels of serum GHBP detected in the patient and his mother. Despite this mutation, the presence of the wild-type GHR allele, presumably, permits some normality in GH-induced action. |
| Databáze: | OpenAIRE |
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