Detection of Growth Hormone Gene Defects by Dideoxy Fingerprinting (ddF)

ICHIRO MIYATA, JOY D. COGAN, MELISSA A. PRINCE, TAKASHI KAMIJO, MASAMICHI OGAWA, JOHN A. PHILLIPS
1997 Endocrine journal  
We carried out screening for mutations in the GH-1 gene in 29 sporadic Japanese subjects with severe Isolated Growth Hormone Deficiency (IGHD) by dideoxy fingerprinting (ddF). Three of 29 (N 10%) were heterozygous 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 transition in the first base of the donor splice site of IVS 3 (+1G--A) and 3) a G-' A
more » ... A) and 3) a G-' A transition in the 183rd codon of the GH-1 mature peptide 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 (+1G-~A) mutation has been previously reported in affected individuals from three unrelated families with IGHD type II (autosomal dominant form). This mutation destroys the GH IVS 3 donor splice site, causing skipping 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 genomic DNAs provides a practical tool to detect GH gene mutations and 2) some sporadic cases of IGHD may be caused by GH gene alternations.
doi:10.1507/endocrj.44.149 pmid:9152628 fatcat:eop5z3s32bcfnlnjezqgyetf6y