Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1981 Oct;78(10):6372–6375. doi: 10.1073/pnas.78.10.6372

Molecular basis for familial isolated growth hormone deficiency.

J A Phillips 3rd, B L Hjelle, P H Seeburg, M Zachmann
PMCID: PMC349041  PMID: 6273867

Abstract

Nuclear DNA from four individuals with familial isolated growth hormone (somatotropin) deficiency (IGHD) type A was studied by restriction endonuclease analysis. By using 32P-labeled human growth hormone (hGH) cDNA sequences as a probe, patterns seen after various digestions indicated that these individuals were homozygous for a deletion of at least 7.5 kilobases (kb) of DNA. This deletion includes the gene that encodes the normal growth hormone but does not include the variant growth hormone gene. Restriction patterns of DNAs from all family members agreed with an autosomal recessive mode of inheritance of the deletion that correlates with the clinical phenotype. Furthermore, independent assortment of the two types of hGH genes suggests that these genes are nonallelic. These findings indicate that, in these families, IGHD type A is caused by deletion of the normal hGH genes and that this disorder can occur in the presence of variant hGH genes.

Full text

PDF
6373

Images in this article

6373Image
on p.6373
6373Image
on p.6373
6374Image
on p.6374
6374Image
on p.6374
6374Image
on p.6374

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BAGLIONI C. The fusion of two peptide chains in hemoglobin Lepore and its interpretation as a genetic deletion. Proc Natl Acad Sci U S A. 1962 Nov 15;48:1880–1886. doi: 10.1073/pnas.48.11.1880. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Embury S. H., Lebo R. V., Dozy A. M., Kan Y. W. Organization of the alpha-globin genes in the Chinese alpha-thalassemia syndromes. J Clin Invest. 1979 Jun;63(6):1307–1310. doi: 10.1172/JCI109426. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Fiddes J. C., Seeburg P. H., DeNoto F. M., Hallewell R. A., Baxter J. D., Goodman H. M. Structure of genes for human growth hormone and chorionic somatomammotropin. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4294–4298. doi: 10.1073/pnas.76.9.4294. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Fritsch E. F., Lawn R. M., Maniatis T. Characterisation of deletions which affect the expression of fetal globin genes in man. Nature. 1979 Jun 14;279(5714):598–603. doi: 10.1038/279598a0. [DOI] [PubMed] [Google Scholar]
  5. George D. L., Phillips J. A., 3rd, Francke U., Seeburg P. H. The genes for growth hormone and chorionic somatomammotropin are on the long arm of human chromosome 17 in region q21 to qter. Hum Genet. 1981;57(2):138–141. doi: 10.1007/BF00282009. [DOI] [PubMed] [Google Scholar]
  6. Illig R. Growth hormone antibodies in patients treated with different preparations of human growth hormone (HGH). J Clin Endocrinol Metab. 1970 Dec;31(6):679–688. doi: 10.1210/jcem-31-6-679. [DOI] [PubMed] [Google Scholar]
  7. Jeffreys A. J., Flavell R. A. A physical map of the DNA regions flanking the rabbit beta-globin gene. Cell. 1977 Oct;12(2):429–439. doi: 10.1016/0092-8674(77)90119-2. [DOI] [PubMed] [Google Scholar]
  8. Kunkel L. M., Smith K. D., Boyer S. H., Borgaonkar D. S., Wachtel S. S., Miller O. J., Breg W. R., Jones H. W., Jr, Rary J. M. Analysis of human Y-chromosome-specific reiterated DNA in chromosome variants. Proc Natl Acad Sci U S A. 1977 Mar;74(3):1245–1249. doi: 10.1073/pnas.74.3.1245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Maniatis T., Kee S. G., Efstratiadis A., Kafatos F. C. Amplification and characterization of a beta-globin gene synthesized in vitro. Cell. 1976 Jun;8(2):163–182. doi: 10.1016/0092-8674(76)90001-5. [DOI] [PubMed] [Google Scholar]
  10. Martial J. A., Hallewell R. A., Baxter J. D., Goodman H. M. Human growth hormone: complementary DNA cloning and expression in bacteria. Science. 1979 Aug 10;205(4406):602–607. doi: 10.1126/science.377496. [DOI] [PubMed] [Google Scholar]
  11. McDonell M. W., Simon M. N., Studier F. W. Analysis of restriction fragments of T7 DNA and determination of molecular weights by electrophoresis in neutral and alkaline gels. J Mol Biol. 1977 Feb 15;110(1):119–146. doi: 10.1016/s0022-2836(77)80102-2. [DOI] [PubMed] [Google Scholar]
  12. Niall H. D., Hogan M. L., Sauer R., Rosenblum I. Y., Greenwood F. C. Sequences of pituitary and placental lactogenic and growth hormones: evolution from a primordial peptide by gene reduplication. Proc Natl Acad Sci U S A. 1971 Apr;68(4):866–870. doi: 10.1073/pnas.68.4.866. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Orkin S. H., Alter B. P., Altay C., Mahoney M. J., Lazarus H., Hobbins J. C., Nathan D. G. Application of endonuclease mapping to the analysis and prenatal diagnosis of thalassemias caused by globin-gene deletion. N Engl J Med. 1978 Jul 27;299(4):166–172. doi: 10.1056/NEJM197807272990403. [DOI] [PubMed] [Google Scholar]
  14. Orkin S. H., Old J., Lazarus H., Altay C., Gurgey A., Weatherall D. J., Nathan D. G. The molecular basis of alpha-thalassemias: frequent occurrence of dysfunctional alpha loci among non-Asians with Hb H disease. Cell. 1979 May;17(1):33–42. doi: 10.1016/0092-8674(79)90292-7. [DOI] [PubMed] [Google Scholar]
  15. Owerbach D., Rutter W. J., Martial J. A., Baxter J. D., Shows T. B. Genes for growth hormone, chorionic somatommammotropin, and growth hormones-like gene on chromosome 17 in humans. Science. 1980 Jul 11;209(4453):289–292. doi: 10.1126/science.7384802. [DOI] [PubMed] [Google Scholar]
  16. Phillips J. A., 3rd, Vik T. A., Scott A. F., Young K. E., Kazazian H. H., Jr, Smith K. D., Fairbanks V. F., Koenig H. M. Unequal crossing-over: a common basis of single alpha-globin genes in Asians and American blacks with hemoglobin-H disease. Blood. 1980 Jun;55(6):1066–1069. [PubMed] [Google Scholar]
  17. Rimoin D. L. Hereditary forms of growth hormone deficiency and resistance. Birth Defects Orig Artic Ser. 1976;12(6):15–29. [PubMed] [Google Scholar]
  18. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  19. Vogelstein B., Gillespie D. Preparative and analytical purification of DNA from agarose. Proc Natl Acad Sci U S A. 1979 Feb;76(2):615–619. doi: 10.1073/pnas.76.2.615. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Zachmann M., Fernandez F., Tassinari D., Thakker R., Prader A. Anthropometric measurements in patients with growth hormone deficiency before treatment with human growth hormone. Eur J Pediatr. 1980 May;133(3):277–282. doi: 10.1007/BF00496089. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES