Novel nonsense mutation (p.Y113X) in the human growth hormone receptor gene in a Brazilian patient with Laron syndrome

• Published in: Arquivos brasileiros de endocrinologia e metabologia 2008-11, Vol.52 (8), p.1264-1271
• Main Authors: Diniz, Erik Trovão, Jorge, Alexander A L, Arnhold, Ivo J P, Rosenbloom, Arlan L, Bandeira, Francisco
• Format: Article
• Language: eng ; por
• Subjects: Carrier Proteins - blood; Child; Codon, Nonsense - genetics; ENDOCRINOLOGY & METABOLISM; Growth Hormone - blood; Homozygote; Humans; Insulin-Like Growth Factor I - analysis; Laron Syndrome - blood; Laron Syndrome - genetics; Male; Membrane Proteins - genetics; Sequence Analysis, DNA
• ISSN: 0004-2730; 1677-9487; 1677-9487; 0004-2730
• DOI: 10.1590/S0004-27302008000800010

To date, about sixty different mutations within GH receptor (GHR) gene have been described in patients with GH insensitivity syndrome (GHI). In this report, we described a novel nonsense mutation of GHR. The patient was evaluated at the age of 6 yr, for short stature associated to clinical phenotype of GHI. GH, IGF-1, and GHBP levels were determined. The PCR products from exons 2-10 were sequenced. The patient had high GH (26 microg/L), low IGF-1 (22.5 ng/ml) and undetectable GHBP levels. The sequencing of GHR exon 5 disclosed adenine duplication at nucleotide 338 of GHR coding sequence (c.338dupA) in homozygous state. We described a novel mutation that causes a truncated GHR and a loss of receptor function due to the lack of amino acids comprising the transmembrane and intracellular regions of GHR protein, leading to GHI.