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

Endocrine Journal

TAKASHI KAMIJO³  MASAMICHI OGAWA²  ICHIRO MIYATA¹  JOHN A. PHILLIPS¹  MELISSA A. PRINCE¹  JOY D. COGAN¹ 

[1] Department of Pediatrics, Vanderbilt University School of Medicine;Nagoya University School of Medicine;Nagoya National Hospital

关键词: Isolated Growth Hormone Deficiency (IGHD);    GH-1 gene;    Dideoxy fingerprinting;    Splicing;   

DOI  :  10.1507/endocrj.44.149

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(20)Cited-By(9)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 (- 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.

【 授权许可】

Unknown