Existence of malfunctioning proα2(I) collagen genes in a patient with a proα2(I)-chain-defective variant of Ehlers-Danlos syndrome

Authors

  • Ryu-Ichiro HATA,

    Corresponding author
    1. Department of Tissue Physiology, Medical Research Institute, Tokyo Medical and Dental University
      Correspondence to R. Hata, Department of Tissue Physiology, Medical Research Institute, Tokyo Medical and Dental University, No. 3–10 Kandasurugadai 2-chome, Chiyodu-ku, Tokyo-shi, Tokyo-to, Japan 101
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  • Shun-ichi KURATA,

    1. Department of Biochemical Genetics, Medical Research Institute, Tokyo Medical and Dental University
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  • Hiroshi SHINKAI

    1. Department of Dermatology, Medical College of Oita
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Correspondence to R. Hata, Department of Tissue Physiology, Medical Research Institute, Tokyo Medical and Dental University, No. 3–10 Kandasurugadai 2-chome, Chiyodu-ku, Tokyo-shi, Tokyo-to, Japan 101

Abstract

Collagen synthesis was examined in skin fibroblasts from a patient with a variant of Ehlers-Danlos syndrome.

The relative rate of collagen synthesis to total protein synthesis in the patient's fibroblasts was always one-half of that in fibroblasts from normal controls. Total collagen synthesis, as assessed by quantification of total hydroxyproline, was also significantly lower than that of controls, indicating that the rate of collagen synthesis by the patient's fibroblasts was decreased compared with that by normal fibroblasts. Analysis of procollagen and collagen components showed the absence of the proα2(I) chain and its derivatives. Dot-blot and Northern-blot analyses showed the patient's fibroblasts to contain less than 10% of the mRNAs for proα2(I) found in control fibroblasts. In spite of these results, Southern blot analysis of genomic DNA indicated the presence of the same number of genes for the proα2(I) collagen chain in the patient's fibroblasts as in control fibroblasts, suggesting malfunctioning proα2(I) collagen genes as the cause for failure of the patient's fibroblasts to synthesize proα2(I) collagen chains.

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