title: Detection of growth hormone gene defects by dideoxy fingerprinting (ddF).
abstract: 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 (approximately 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 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.
authors.affiliation: Department of Pediatrics, Vanderbilt University School of Medicine 37232-0146, USA.
authors.forename: I
authors.initials: I
authors.lastname: Miyata
authors.forename: J D
authors.initials: JD
authors.lastname: Cogan
authors.forename: M A
authors.initials: MA
authors.lastname: Prince
authors.forename: T
authors.initials: T
authors.lastname: Kamijo
authors.forename: M
authors.initials: M
authors.lastname: Ogawa
authors.forename: J A
authors.initials: JA
authors.lastname: Phillips
mesh_terms: D001345:Autoradiography; D001483:Base Sequence; D016172:DNA Fingerprinting; D017931:DNA Primers / Q000737:chemistry; D006130:Growth Disorders / Q000235:genetics*; D019382:Human Growth Hormone / Q000172:deficiency* / Q000235:genetics*; D006801:Humans; D007564:Japan; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012016:Reference Values; D017422:Sequence Analysis, DNA
chemical_list: D017931:DNA Primers; D019382:Human Growth Hormone