Argl83His, a New Mutational “Hot-Spot” in the Growth Hormone (GH) Gene Causing Isolated GH Deficiency Type II

Abstract

Autosomal dominant familial isolated growth hormone (GH) deficiency (IGHD type II) is a rare cause of human GH deficiency. Virtually all reported instances have been due to mutations of the GH gene (GH1) donor splice site at the junction of exon 2 and intron 3 (intervening sequence 3, or IVS3). The biological mechanisms by which such mutations of a single allele result in a functional deficiency state (Le. dominantnegative effects on the normal allele) have not been elucidated. Here we report four unrelated families with IGHD type II caused by a novel missense transition mutation, G6664A, which replaces arginine at position 183 with histidine (ArgI83His, or R183H) in exon 5 of GH1. © 2000, by Walter de Gruyter GmbH & Co. All rights reserved.