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[Phenotype-genotype relations in growth hormone insensitivity]
M O Savage1, K A Woods, A J Clark
1Service d'endocrinologie pédiatrique, St Bartholomew's hospital, London, France.
Summary
Growth hormone (GH) insensitivity stems from GH receptor or IGFI gene mutations, causing varied growth and biochemical phenotypes. This study analyzes 82 patients, revealing diverse clinical presentations and genetic causes.
Area of Science:
- Endocrinology
- Genetics
- Pediatric Growth Disorders
Background:
- Growth hormone (GH) insensitivity presents a spectrum of clinical and biochemical phenotypes.
- It is often linked to mutations in the GH receptor gene or, more recently, the IGFI gene.
Observation:
- This study analyzed 82 patients with GH insensitivity from 23 countries, with a mean age of 8.25 years.
- Mean height SDS was -6.09, and IGFBP3 SDS was -7.99.
- Twenty-three percent of patients were GH binding protein (GHBP) positive, showing significantly better height SDS compared to GHBP negative patients (p < 0.001).
Findings:
- Fifteen distinct GH receptor gene mutations were identified in 27 patients, with no correlation to height or IGFBP-3 SDS.
- A novel phenotype associated with a partial IGFI gene deletion (exons 4 and 5) was described in a 15-year-old boy.
- This boy exhibited severe intrauterine growth retardation, poor postnatal growth, deafness, and mild intellectual disability, with undetectable IGF-I and no response to GH treatment.
Implications:
- GH insensitivity encompasses a wide range of clinical and biochemical variations.
- Genetic analysis of GH receptor and IGFI genes is crucial for diagnosing and understanding GH insensitivity.
- Further research is needed to elucidate the full spectrum of GH insensitivity phenotypes and their underlying genetic mechanisms.