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The growth response to growth hormone (GH) treatment in children with isolated GH deficiency is independent of the presence of the exon 3-minus isoform of the GH receptor.

CONTEXT
A variant of the human GH receptor (GHR) lacks a 22-amino-acid sequence derived from exon 3 (d3-GHR). It was reported that pediatric patients, born small for gestational age or with idiopathic short stature who were homozygous or heterozygous for this variant responded better to GH treatment than those homozygous for the full-length allele (fl-GHR).


OBJECTIVE
The objective was to study the impact of the GHR genotype on the phenotype and growth response in patients with isolated GH deficiency (IGHD) treated with GH.


DESIGN
This was a retrospective, multinational, multicenter observational study.


PATIENTS
Patients with IGHD (n = 107) were recruited.


INTERVENTIONS
All patients received GH treatment at replacement doses. The GHR genotype (fl-GHR/fl-GHR, fl-GHR/d3-GHR, or d3-GHR/d3-GHR) was determined by PCR amplification.


MAIN OUTCOME MEASURES
Measures included height sd score, height velocity, height velocity sd score at baseline and 1 yr of GH treatment, and their changes.


RESULTS
There was no statistically significant difference of the main outcome measures between patients with the d3-GHR allele (n = 48) and patients who were homozygous for the fl-GHR allele (n = 59). Moreover, the genotype group did not contribute significantly to the growth prediction in multiple linear regression models.


CONCLUSIONS
Our results indicate that the d3-GHR allele does not affect response to GH treatment or contribute to growth predictions in patients with IGHD who received replacement doses of GH aiming to restore a normal GH status. We did not confirm the previously reported data obtained in patients small for gestational age or with idiopathic short stature who received supraphysiological GH doses.