Summary
We studied four Japanese patients with isolated growth hormone (hGH) deficiency from three different families. There was consanguinity in two of the three families, and three patients were second cousins. Each patient was homozygous for a deletion of approximately 7.5 kilobases, which included the hGH-N gene. The deletions in three patients belonging to two different families were associated with the same restriction fragment length polymorphism haplotype, while the deletion of the other patient was associated with a different haplotype. All patients were treated with injections of pituitary hGH. The response to the therapy differed among them, that is, two patients belonging to different families showed a poor response together with the presence of anti-hGH antibodies, while the other two patients belonging to the same family showed a rather good response together with the absence of such antibodies. It is suggested that the production of anti-hGH antibodies is not solely due to the gene deletion, but that an unknown immunological disposition might also be involved.
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Brager, S., Phillips, J.A., III, Joss, E., Schwarz, H., and Zuppinger, K. 1985. A new type of familial growth hormone deficiency due to a 8.5 kb deletion within the growth hormone gene cluster. InEndocrine Genetics and Genetics of Growth.Progress in Clinical Biological Research, Vol. 200, Papadatos, C.J., and Bartsocas, C.S., eds., Alan R. Liss Inc., New York, pp. 103–111.
Goossens, M., Brauner, R., Czernichow, P., Duquesnog, P., and Rappaport, R. 1986. Isolated growth hormone (GH) deficiency Type 1A associated with a double deletion in the human GH gene cluster.J. Clin. Endocrinol. Metab. 62:712–716.
Illig, R. 1970. Growth hormone antibodies in patients treated with different preparations of human growth hormone (hGH).J. Clin. Endocrinol. Metab. 31:679–688.
Illig, R., Prader, A., Ferrandez, M., and Zachman, M. 1971. Hereditary prenatal growth hormone deficiency with increased tendency to growth hormone antibody formation, A-type of isolated growth hormone deficiency.Acta Pediatr. Scand. 60(Suppl.):607.
Kunkel, L.M., Smith, K.D., Boyer, S.H., Borgaonkar, D.S., Wachtel, S.S., Miller, O.J., Berg, W.R., Jones, H.W., Jr., and Rary, J.M. 1977. Analysis of human Y-chromosome specific reiterated DNA in chromosome variants.Proc. Natl. Acad. Sci. U.S.A. 74:1245–1249.
Laron, Z., Kelijman, M., Pertzelan, A., Keret, R., Shoffner, J.M., and Parks, J.S. 1985. Human growth hormone gene deletion without antibody formation or growth arrest during treatment—A new disease entity?Isr. J. Med. Sci. 21:999–1006.
Matsuda, I., Yamamoto, J., Nagata, N., Ninomiya, N., Akaboshi, H., Ohtsuka, H., and Katsuki, T. 1977. Cytosomal enzyme activities in cultured lymphoid cells lines.Clin. Chim. Acta 80:483–486.
Mori, T., Naito, H., Nishikawa, H., Arakawa, K., Yoshida, Y., Takeuchi, S., and Akabane, T. 1981. Lipoatrophy observed during hGH therapy in a case of isolated growth hormone deficiency type A (Illig).Shonika Shinryo (in Japanese)44:2035–2040.
Nishi, Y., Aihara, K., Usui, T., Phillips, J.A., III, Mallonee, R.L., and Migeon, C.J. 1984. Isolated growth hormone deficiency type 1A in a Japanese family.J. Pediatr. 104:885–889.
Phillips, J.A., III, Hjelle, B.L., Seeburg, P.U., and Zackmann, M. 1981. Molecular basis for familial isolated growth hormone deficiency.Proc. Natl. Acad. Sci. U.S.A. 78:6372–6375.
Phillips, J.A., III. 1983. The growth hormone (hGH) gene and human disease. InBanbury Report 14. Recombinant DNA: Applications to Human Disease, Caskey, C.T., and White, R., eds., Cold Spring Harbor Laboratory, New York, pp. 305–315.
Rivarola, M.A., Phillips, J.A., III, Migeon, C.J., Heinrich, J.J., and Hjelle, B.L. 1984. Phenotypic heterogeneity in familial isolated growth hormone deficiency type 1-A.J. Clin. Endocrinol. Metab. 59:34–40.
Roth, J., Glick, S.M., Yalow, R.S., and Berson, S.A. 1964. Antibodies to human growth hormone (hGH) in human subjects treated with hGH.J. Clin. Invest. 43:1056–1065.
Seeburg, P.H. 1982. The human growth hormone gene family: Nucleotide sequences show recent divergence and predict a new polypeptide hormone.DNA 1:239–249.
Southern, E.M. 1975. Detection of specific sequence among DNA fragments separated by gel electrophoresis.J. Mol. Biol. 98:503–517.
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Matsuda, I., Hata, A., Jinno, Y. et al. Heterogeneous phenotypes of Japanese cases with a growth hormone gene deletion. Jap J Human Genet 32, 227–235 (1987). https://doi.org/10.1007/BF01876877
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DOI: https://doi.org/10.1007/BF01876877
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