We carried out screening for mutations in the GH-1 gene in 29 sporadic
Japanese subjects with severe Isolated Growth Hormone Deficiency (IGH
D) by dideoxy fingerprinting (ddF). Three of 29 (10%) were heterozygou
s for each of the following GH-1 gene mutations including: 1) an G -->
A transition in the third codon of the GH-1 signal peptide of exon 1
resulting in a Threonine to Alanine substitution, 2) a G --> A transit
ion in the first base of the donor splice site of IVS 3 (+1G --> A) an
d 3) a G --> A transition in the 183rd codon of the GH-1 mature peptid
e of exon 5 resulting in an Arginine to Histidine substitution. One of
three was heterozygous for both mutations of 1) and 2). The IVS 3 (+1
G --> A) mutation has been previously reported in affected individuals
from three unrelated families with IGHD type II (autosomal dominant f
orm). This mutation destroys the GH IVS 3 donor splice site, causing s
kipping of exon 3 and loss of the codons for amino acids 32-71 of the
mature GH peptide. Our findings indicate that 1) ddF screening of geno
mic DNAs provides a practical tool to detect GH gene mutations and 2)
some sporadic cases of IGHD may be caused by GH gene alternations.