Prevalence of GH-1 Gene Deletion in Patients with Isolated Growth Hormone Deficiency in Japan

Endocrine Journal

TAKASHI KAMIJO⁷  YOSHIKAZU NISHI¹  MASAMICHI OGAWA⁶  JUNICHI KOGA⁴  YUTAKA IGARASHI⁵  OTHER MEMBERS OF THE GH GENE STUDY GROUP⁶  NORITAKA IWATANI²  HITOSHI KOHNO³  Young Jin BYUN⁴ 

[1] Department of Pediatrics, Hiroshima Red Cross Hospital;Department of Child Development, Kumamoto University School of Medicine;Division of Endocrinology and Metabolism, Fukuoka Children's Hospital;Laboratories for Bioengineering and Research, JCR Pharmaceuticals Co., Ltd.;Department of Pediatrics, Tohoku University School of Medicine;Department of Pediatrics, Nagoya University School of Medicine;Department of Pediatrics, Nagoya National Hospital

关键词: Isolated growth hormone deficiency (IGHD);    IGHD type IA;    GH-1 gene;    Polymerase chain reaction (PCR);    Deletion mutation;   

DOI  :  10.1507/endocrj.47.157

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(13)Cited-By(5)A multicenter study was carried out to investigate the prevalence of growth hormone (GH-1) gene deletions among patients with isolated growth hormone deficiency (IGHD) and extremely short stature in Japan, using PCR method. Genomic DNA was extracted from the whole blood samples of 48 patients (34 males and 14 females) at 20 hospitals. All the patients fulfilled the inclusion criteria as follows: (1) IGHD patients whose every peak serum GH level in more than two tests <5ng/ml and (2) pretreatment height <-3SD, regardless of family history and facial feature characteristic of GH-1 gene deletion. The subjects were screened for deletions in GH-1 gene, using a PCR method that could identify deletions of 6.7, 7.0 and 7.6kbp. Three (6.25%) out of 48 subjects were found to have such deletion fragments. The first case was a boy homozygous for deletion of 6.7kbp fragments. The second case was a girl heterozygous for 6.7kbp deletion. A direct sequence analysis revealed a 2-bp deletion in exon 3 on the remaining allele that created a stop codon in exon 4. The third case was a boy also heterozygous for 6.7kbp deletion. By direct sequencing analysis, three point mutations were detected in the promoter region on the opposite allele together with a four-base addition at base 250. One of the mutations was in the area of Pit-1 binding site (at base -123). The latter two cases apparently represent new types of compound heterozygote of GH-1 gene deletion. Our results suggest that GH-1 gene mutation is not so rare in extremely short IGHD children in Japan.

【 授权许可】

Unknown