Background: Four distinct familial types of isolated GH deficiency (IGHD) have been described so far. Objective: We report a novel nonsense GH1 mutation in a father and a son. Patients: Father’s height was 137.3 cm (–6.79 SDS); mother’s height was 157.3 cm (–1.86 SDS). By the age of 8.25 years, his height was 104.3 cm (–4.82 SDS) and his weight was 18.3 kg (–3.35 SDS). GH stimulation tests had low peak GH value of 6.5 ng/ml (proband) and 6.3 ng/ml (father). Other pituitary hormones and magnetic resonance imaging (MRI) of the pituitary region was normal in both patients. The proband received recombinant human GH (rhGH) treatment (30 µg/kg/day) and he grew 15.4 cm in 15 months. Results: Sequencing of the GH1 gene revealed a novel heterozygous nonsense mutation in both the father and the son (c.199A>T), which introduces a stop codon in exon 3. Conclusion: We present a family with IGHD II, with severe short stature, no phenotypic characteristics of GHD and a novel nonsense mutation in exon 3 of the GH1 gene. As fibroblasts were unavailable, we used computer analysis and we propose a unique mechanism that combines aberrant splicing and derogated GH release from the pituitary with residual secretion of a bioinactive truncated GH peptide.

Keywords:
Novel nonsense mutation, Isolated growth hormone deficiency type II, Aberrant splicing, Bioinactive truncated GH
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2011
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