ABSTRACT
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.
