Atypical GH insensitivity syndrome and severe insulin-like growth factor-I deficiency resulting from compound heterozygous mutations of the GH receptor, including a novel frameshift mutation affecting the intracellular domain
| Autor: | Ron G. Rosenfeld, Javier Aisenberg, Vivian Hwa, Rachel Sugalski, Rachel Rothenberg, Valerie Auyeung, Michael A. Derr, Helio Pedro, Amy Chartoff |
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| Rok vydání: | 2010 |
| Předmět: |
Proband
Male medicine.medical_specialty Endocrinology Diabetes and Metabolism Molecular Sequence Data Growth hormone receptor Biology Compound heterozygosity medicine.disease_cause Short stature Polymerase Chain Reaction law.invention Frameshift mutation Exon Endocrinology law Internal medicine medicine Humans Point Mutation Amino Acid Sequence Insulin-Like Growth Factor I Frameshift Mutation Growth Disorders Mutation Human Growth Hormone DNA Receptors Somatotropin Sequence Analysis DNA Child Preschool Pediatrics Perinatology and Child Health Recombinant DNA Female medicine.symptom Carrier Proteins |
| Zdroj: | Hormone research in paediatrics. 74(6) |
| ISSN: | 1663-2826 |
| Popis: | Background/Aims: GH insensitivity and IGF deficiency may result from aberrations of the GH receptor (GHR). We describe a 4-year-old child with modest growth failure and normal serum concentrations of GH-binding protein (GHBP), but clinical evidence of GH insensitivity. Method: Serum and DNA samples from the proband and his parents were analyzed. Results: The child had a height of –4 SD, elevated serum GH concentrations, abnormally low serum IGF-I and IGFBP-3 concentrations and normal GHBP concentrations. DNA analysis revealed compound heterozygosity for mutations of GHR, including a previously reported R211H mutation and a novel duplication of a nucleotide in exon 9 (899dupC), the latter resulting in a frameshift and a premature stop codon. Treatment with recombinant DNA-derived IGF-I resulted in growth acceleration. Conclusion: Mutations affecting the intracellular domain of the GHR can result in GH insensitivity and IGF deficiency, despite normal serum concentrations of GHBP. The presence of clinical and biochemical evidence of GH resistance is sufficient to consider the possibility of aberrations of the GHR, even in the presence of normal serum GHBP concentrations. |
| Databáze: | OpenAIRE |
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