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1991 Fiscal Year Final Research Report Summary

Molecular and gentic analysis of receptor for 1, 25-dihydroxyvitamin D in patients with vitamin D-dependent rickets type II

Research Project

Project/Area Number 02670444
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Pediatrics
Research InstitutionThe University of Tokushima

Principal Investigator

TAKEDA Eiji  University of Tokushima, School of Medicine Assistant Professor, 医学部, 講師 (00144973)

Co-Investigator(Kenkyū-buntansha) KURODA Yasuhiro  University of Tokushima, School of Medicine Professor, 医学部, 教授 (20035471)
Project Period (FY) 1990 – 1991
KeywordsVitamin D-dependent rickets type II / Vitamin D receptor / Genetic mutation / Congenital metabolic disease / 1, 25-Dihydroxyvitamin D
Research Abstract

Vitamin D-dependent rickets type II is a hereditary disease resulting from a defective vitamin D receptor. We suggested that this disease was an autosomal recessive disorder by showing intermediate levels of 25-hydroxyvitamin D-24-hydroxylase induction in the parents. Therefore, it would be important to identify genetic defects causing the disease and to detect heterozygous carriers at the molecular level. In six patients with vitamin D-d. ependent rickets type II whose fibroblasts displayed normal cytosol binding and impaired nuclear uptake of 1, 25-dihydroxyvitamin D_3, western, Southern, and northern analyses failed to disclose any abnormalities in vitamin D_3 receptor protein and its gene. Exons 2 and 3 of the vitamin D receptor CDNA, which er), code the DNA-binding domain consisting of two zinc fingers, -were amplified by PCR and sequenced to identify the specific mutation in the vitamin D receptor gene. In the three patients and one normal control a T-to-C transition was found in the putative initiation codon, while this transition was not observed in another normal control. This finding suggested that an original initiation codon was located at position 10-12 in the human vitamin D receptor CDNA sequence reported previously. In contrast, a unique G-to-A transition at position 140 in exon 3, resulting in substitution of arginine by glutamine at residue 47, was-revealed only-in these three patients. The arginine at 47 is located between two zinc fingers and is conserved within all steroid hormone receptors. Therefore, it is highly conceivable that this amino acid substitution is responsible for the defect of vitamin D receptor in the patients. Single-strand conformation polymorphism analysis of amplified DNA confirmed that all patients were homozygous and that parents from one family were heterozygous carriers for this mutation.

  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Takeda Eiji: "25-Hydroxyvitamin D-24-hydroxylase in phytohemagglutinin-stimulated lymphocytes:Intermediate bioresponse to 1,25-dihydroxy-vitamin D_3 of cells from parents of patients with vitamin D-dependent rickets type II" Journal of Clinical Endocrinology and Metabolism. 70. 1068-1074 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takeda Eiji: "Effect of long-term treatment with massive doses of 1-hydroxy-vitamin D_3 on calcium-phosphate balance in patients with vitamin D-dependent rickets type II" Acta Paediatrica Japonica. 32. 39-43 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 横田 一郎: "ビタミンD依存性くる病II型患者の培養皮膚線維芽細胞における1,25ーdihydroxy vitamin D受容体の研究" 日本小児科学会雑誌. 94. 215-223 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 横田 一郎: "ビタミンD依存性くる病II型の遺伝形式に関する研究" 日本小児科学会雑誌. 94. 955-960 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 武田 英二: "禿頭を伴うビタミンD依存性くる病II型の臨床生化学的検討" 日本先天代謝異常学会雑誌. 6. 24-31 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 武田 英二: "ビタミンD依存性くる病II型の遺伝性に関する研究" ホルモンと臨床 特集/小児内分泌学の進歩'90. 38. 1203-1206 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yokota Ichiro: "Clinical and biochemical findings in parents of children with vitamin D-dependent rickets type II" Journal of Inherited Metabolic Disease. 14. 231-240 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Saijo Takahiko: "A unique mutation in the vitamin D receptor gene in three Japanese patients with vitamin D-dependent rickets typr II:Utility of single-strand conformation polymorphism analysis for heterozygous carrier detection" American Journal of Human Genetics. 49. 668-673 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Arase Seiji: "The effect of 1,25-dihydroxyvitamin D_3 on the growth and differentiation of cultured human outer root sheath cells from normal subjects and patients with vitamin D-dependent rickets type II with alopecia" Journal of Dermatological Science. 2. 353-360 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 西條 隆彦: "ビタミンD依参性くる病II型におけるビタミンD受容体蛋白および遺伝子の解析" 日本小児科学会雑誌. 95. 1772-1777 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 武田 英二: "ビタミンD依存症" 小児内科. 23. 697-701 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 武田 英二: "ビタミンD依存性くる病II型" 小児内科. 23. 1779-1783 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 武田 英二: "ビタミンD受容体ー遺伝子診断によるビタミンD依存性クル病II型のスクリ-ニングー" THE BONE. 5. 53-57 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takeda, E., Yokota, I., Ito, M., Kobashi, H., Saijo, T., Kuroda, Y: "25-Hydroxyvitamin D-24-hydroxylase in phytohemaggulutinin-stimulated lymphocytes : Intermediate bioresponse to 1, 25-dihydroxyvitamin D_3 of cells from parents of patients with vitamin D-dependent rickets type II" J Clin Endocrinol Metab. 70. 1068-1074 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takeda, E., Yokota, I., Saijo, T., Kawakami, I., Ito, M., Kuroda, Y: "Effect of long-term treatment with massive doses of 1 -hydroxyvitamin D_3 on calcium-phosphate balance in patients with vitamin D-dependent rickets type II" Acta Paediatr Jpn. 32. 39-43 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yokota, I., Takeda, E.: "Characterization of the receptor proteins for 1, 25-dihydroxyvitamin D_3 in the cultured skin fibroblasts from five patients with vitamin D-dependent rickets type II" Nihon Syounika Gakkai Zasshi. 94. 215-223 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yokota, I., Takeda, E.: "Examinations of the receptor system for 1, 25-dihydroxyvitamin D_3 in the parents of patients with vitamin D-dependent rickets type II - Evidence of the autosomal recessive inheritance -" Nihon Syounika Gakkai Zasshi. 94. 955-960 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] "Clinical and biochemical investigations in the patients with vitamin D-dependent rickets type II" Nihon Sententaisyajou Gakkai Zasshi. 6. 24-31 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] "Inheritance of vitamin D-dependent rickets type II" Horumon to tinsyou. 38. 1203-1206 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yokota, I., Takeda, E., Ito, M., Kobashi, H., Saijo, T., Kuroda, Y.: "Clinical and biochemical findings in parents of children with vitamin D-dependent rickets type II" J Inher Metab Dis. 14. 231-240 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Saijo, T. Ito, M., Takeda, E., Huq, A. H. M. M., Naito, E., Yokota, I., Sone, T., Pike, J. W., Kuroda, Y: "A unique mutation in vitamin D receptor gene in three Japanese patients with vitamin D-dependent rickets type II and utility of single-strand conformation polymorphism analyis for heterozygous carrier detection" Amer J Hum Genet. 49. 668-673 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Arase, S., Sadamoto, Y., Kuwana, R., Nakanishi, H., Fujie, K., Takeda, K., Takeda, E: "The effect of 1, 25-dihydroxy vitamin D_3 on the growth and differentiation of cultured human outer root sheath cells from subjects and patients with vitamin D-dependent rickets type II with alopecia" J Dermatol Sci. 2. 353-360 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Saijo, T., Ito, M., Takeda, E: "Molecular analysis of vitamin D receptor in patients with vitamin D-dependent rickets type II" Nihon Syounika Gakkai Zasshi. 95. 1772-1777 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takeda, E., Saijo, T: "Vitamin D dependency" Syouninaika. 23. 697-701 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takeda, E., Saijo, T., Ito, M.: "Vitamin D-dependent rickets type II" Syouninaika. 23. 1779-1783 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takeda, E., Saijo, T., Ito, M.: "Vitamin D receptor : Screening of the mutations in vitamin D-dependent rickets type II" The Bone. 12. 53-57 (1991)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1993-03-16  

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