摘要
利用DNA诊断技术,对正常人及16例侏儒症患者外周血白细胞DNA生长激素基因簇进行分析,在中国人种中首次发现2例患者(系同胞姐妹)为缺失包括hGH-N基因在内的7.1kbDNA片段的纯合子。患者的双亲、祖母及外祖母为携带缺失基因的杂合子,但表型正常;患者的祖父及外祖父为正常的纯合子,此疾病为常染色体隐性遗传病。其他14例患者均未发现hGH-N基因的缺失。对绒毛DNA分析结果表明与正常人白细胞DNA是一致的。这一方法在优生学上可作产前及婚前诊断,避免hGH-N基因缺失的纯合子出生。
The structure of human growth hormone gene cluster on DNAs from normal individuals and dwarfs was analyzed by using Southern blot assay. Six bands, namely 8.3, 6.7, 5.3, 3.8, 3.0 and 1.2kb were shown in the autoradiograph of normal genomic DNAs (WBC and chorion) digested with BamH I and hybridized with 32P-hGH cDNA. These bands corresponded to human chorionic somatomammotropin-L gene(hCS-L),-B gene (hCS-B),-A gene (hCS-A),human growth hormone-normal gene (hGH-N), part of human growth hormone-variant gene (hGH-V) and another part of hGH-V gene respectively. While 3 bands were shown when digested with Hind III, namely 25, 21.3, 14.8kb which corresponded to hGH-N + hCS-L, hGH-V + hCS-B and hCS-A respectively. The autoradiograph patterns of BamH I fragment from the genomic DNAs of two affected siblings showed that the 3.8kb fragment containing hGHrN gene which encoded human growth hormone was missed completely. The patterns of Hind III fragment revealed that the 25kb fragment was missing, but 21.3kb and 14.8kb fragments were still retained, and a new 17.9 kb fragment was generated which was due to a deletion of 7.1 kb from the normal 25kb fragment. The results indicated that the two affected siblings were homozygous for a deletion of 7.1kb. The Southern blot data from the family members of the affected siblings indicated the parents and grandmothers of the patients were heterozygous with one normal and one deleted hGH-N alleles. But the grandfathers were normal homozygotes. Pedigree analysis and data of genotypies and phenotypies from the family members suggested the IGHD IA was an autosomal recessive hereditary disease.
The familial IGHD with deletion hGH-N gene we found is the first family reported, in China. The DNA diagnosis of IGHD can be used both in prenatal and premarriage exams to avoid the birth of diseased children.
出处
《中华内分泌代谢杂志》
CAS
CSCD
北大核心
1989年第1期3-6,共4页
Chinese Journal of Endocrinology and Metabolism
基金
卫生部75攻关项目
关键词
侏儒
生长激素缺乏
生长激素
Isolated growth hormone deficiency Human growth hormone gene deletion
