Two different 5' splice site mutations in the growth hormone gene causing autosomal dominant growth hormone deficiency

Four distinct types of isolated growth hormone deficiency (IGHD) have been described to date. Of these IGHD type II has been defined as having a dominant mode of inheritance. We performed a molecular genetic analysis of two patients clinically characterized as IGHD type II. One of the patients and her father shared a heterozygous G-A transition in the first 5' donor splice site of intron III. The second father and daughter studied also showed a heterozygous G-A transition in the fifth base from the 5' donor splice site in the same intron. Both mutations altered the correct splicing of the growth hormone pre-mRNA when the corresponding genes were expressed in COS-7 cells. We propose that both inherited mutations are responsible for IGHD type II in these patients.