Disruption of exon definition produces a dominant-negative growth hormone isoform that causes somatotroph death and IGHD II.

Isolated growth hormone deficiency type II (IGHD II) is characterized by short stature due to dominant-negative mutations of the human growth hormone gene (GH1). Most of the known mutations responsible for IGHD II cause aberrant splicing of GH1 transcripts. We have recently shown that mutations that cause exon 3 skipping and produce a dominant-negative 17.