2 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 havi ng a dominant mode of inheritance. We performed a molecular genetic an alysis of two patients clinically characterized as IGHD type II. One o f 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 da ughter 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 c orresponding genes were expressed in COS-7 cells. We propose that both inherited mutations are responsible for IGHD type II in these patient s.