Novel compound heterozygous mutations of the growth hormone-releasing hormone receptor gene in a case of isolated growth hormone deficiency
| Autor: | Yumi Asakura, Akiko Soneda, Koji Muroya, Mitsuo Itakura, Hiroshi Inoue, Masaki Takagi, Masanori Adachi, Tomonobu Hasegawa |
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| Rok vydání: | 2012 |
| Předmět: |
Receptors
Neuropeptide medicine.medical_specialty Heterozygote Growth-hormone-releasing hormone receptor Endocrinology Diabetes and Metabolism medicine.medical_treatment RNA Splicing Blotting Western Molecular Sequence Data Dwarfism Fluorescent Antibody Technique Biology Compound heterozygosity medicine.disease_cause Growth Hormone-Releasing Hormone Short stature Polymerase Chain Reaction Endocrinology Receptors Pituitary Hormone-Regulating Hormone Internal medicine medicine Humans Amino Acid Sequence Receptor Dwarfism Pituitary Luciferases Cell Proliferation Mutation Sequence Homology Amino Acid Growth factor medicine.disease Child Preschool Mutagenesis Site-Directed Female medicine.symptom Minigene |
| Zdroj: | Growth hormoneIGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. 23(4) |
| ISSN: | 1532-2238 |
| Popis: | Objective To elucidate the pathogenesis of isolated growth hormone (GH) deficiency in a Japanese girl without consanguinity. Design A 2-year-old girl of height 77.2cm (−3.0 SD for Japanese girls) was found to have an insulin-like growth factor (IGF)-1 level of 7ng/mL and IGF binding protein-3 (IGFBP-3) level of 0.41μg/mL. GH responded modestly to a series of pharmacological stimulants, increasing to 2.81ng/mL with insulin-induced hypoglycemia, 3.78ng/mL with arginine, and 3.93 with GH-releasing hormone (GHRH). Following direct sequencing of the GHRH receptor ( GHRHR ) gene, evaluation by the luciferase reporter assay, immunofluorescence study, and in vitro splicing assay with minigene constructs was conducted. Results Novel compound heterozygous GHRHR gene mutations were identified in the patient. A p.G136V substitution elicited no luciferase activity increment in response to GHRH stimulation, with normal membranous expression. Splicing assay demonstrated that the IVS2+3a>g mutation would lead to aberrant splicing. Conclusions A case of isolated GH deficiency due to novel GHRHR gene mutations was identified. |
| Databáze: | OpenAIRE |
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