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Kowarski syndrome〔(OMIM Database entry for Kowarski syndrome )〕 describes cases of growth failure (height and bone age two standard deviations below the mean for age), despite the presence of normal or slightly high blood growth hormone by radioimmunoassay (RIA-GH) and low serum IGF1 (formerly called somatomedin), and who exhibit a significant increase in growth rate following recombinant GH therapy. == Cause == Allen Avinoam Kowarski et al.〔Kowarski, A. A., Schneider, J. J., Ben-Galim, E., Weldon, V. V., Daughaday, W. H. Growth failure with normal serum RIA-GH and low somatomedin activity: somatomedin restoration and growth acceleration after exogenous GH. J. Clin. Endocr. 47: 461-464,1978.〕 described the first two cases of the Kowarski syndrome in 1978. The group speculated that their patients' growth impairment was caused by a mutation in the growth hormone gene, which altered the structure of their secreted growth hormone, reducing its biological activity while retaining its ability to bind the antibodies used in the RIA-GH. Their RIA-GH measured growth hormone of reduced bioactivity. The children retained the ability to respond to treatment with active growth hormone. The speculation of Kowarski et al. was confirmed by Valenta et al in 1985, Takahshi et al in 1996 and 1997 and Besson et al in 2005. Valenta et al〔Valenta, L. J., Sigel, M. B., Lesniak, M. A., Elias, A. N., Lewis, U. J., Friesen, H. G., Kershnar, A. K. Pituitary dwarfism in a patient with circulating abnormal growth hormone polymers. New Eng. J. Med. 312: 214-217,1985.〕 studied a case of Kowarski syndrome where they confirmed a structural abnormality of the growth hormone molecule. 60 to 90% of circulating growth hormone of the patient was in the form of tetramers and dimers (normal, 14% to 39% in plasma) and the patients' growth hormone polymers were abnormally resistant to conversion into monomers by urea. Takahashi et al.〔Takahashi, Y., Kaji, H., Okimura, Y., Goji, K., Abe, H., Chihara, K. Short stature caused by a mutant growth hormone. New Eng. J. Med. 334: 432-436, 1996. Note: Erratum: New Eng. J. Med. 334: 1207,1996.〕 reported a case of a boy with short stature who was heterozygous for a mutation in the GH1 gene. In this child, growth hormone not only could not activate the GH receptor (GHR) but also inhibited the action of wild type GH because of its greater affinity for GHR and GH-binding protein (GHBP) that is derived from the extracellular domain of the GHR. Thus, a dominant-negative effect was observed. Takahashi et al.〔Takahashi, Y., Shirono, H., Arisaka, O., Takahashi, K., Yagi, T., Koga, J., Kaji, H., Okimura, Y., Abe, H., Tanaka, T., Chihara, K. Biologically inactive growth hormone caused by an amino acid substitution. J. Clin. Invest. 100: 1159-1165,1997.〕 demonstrated in a girl with short stature, a biologically inactive growth hormone resulting from a heterozygous mutation in the GH1 gene. At age 3 years, the girl's height was 3.6 standard deviations below the mean for age and sex. Bone age was delayed by 1.5 years. She had a prominent forehead and a hypoplastic nasal bridge with normal body proportions. She showed lack of growth hormone action despite high immunoassayable GH levels in serum and marked catch-up growth to exogenous GH administration. Results of other studies were compatible with the production of a bioinactive GH, which prevented dimerization of the growth hormone receptor, a crucial step in GH signal transduction. Besson et al〔Besson, A., Salemi, S., Deladoey, J., Vuissoz, J.-M., Eble, A., Bidlingmaier, M., Burgi, S., Honegger, U., Fluck, C., Mullis, P. E. Short stature caused by a biologically inactive mutant growth hormone (GH-C53S). J. Clin. Endocr. Metab. 90: 2493-2499, 2005.〕 described in 1955 a Serbian patient with Kowarski syndrome who was homozygous for a mutation in the GH1 gene that disrupted the first disulfide bridge in growth hormone. The parents were each heterozygous for the mutation and were of normal stature. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Kowarski syndrome」の詳細全文を読む スポンサード リンク
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