Journal of Bone and Mineral Metabolism

, Volume 28, Issue 5, pp 585–590 | Cite as

A novel nonsense mutation in the DMP1 gene in a Japanese family with autosomal recessive hypophosphatemic rickets

  • Ryusuke Koshida
  • Hideki Yamaguchi
  • Koji Yamasaki
  • Wakaba Tsuchimochi
  • Tadato Yonekawa
  • Masamitsu Nakazato
Original Article


Autosomal recessive hypophosphatemic rickets (ARHR) is an extremely rare disorder of autosomal recessive inheritance, characterized by hypophosphatemia resulting from renal phosphate wasting. Dentin matrix protein 1 (DMP1), a noncollagenous extracellular protein, plays critical roles in bone mineralization and phosphate homeostasis. Recently, loss-of-function mutations in DMP1 gene have been identified as the molecular cause of ARHR. Here, we describe a Japanese family that includes two ARHR-affected siblings carrying a novel mutation of the DMP1 gene. The patients were a 53-year-old woman and a 50-year-old man with short stature and skeletal deformities who were the offspring of a first-cousin marriage. Biochemical examination revealed hypophosphatemia with renal phosphate excretion and low levels of 1,25(OH)2D. Serum calcium, parathyroid hormone, and urinary calcium excretion were within the normal range, leading to clinical diagnosis of ARHR. Sequence analysis of peripheral leukocytes from the patients revealed that they carried a novel homozygous nonsense mutation in the DMP1 gene (98G>A, W33X), which leads to a truncated DMP protein with no putative biological function. Unaffected family members were heterozygous for the mutation. This is the first report of a Japanese family with ARHR carrying a novel mutation of the DMP1 gene.


Autosomal recessive hypophosphatemic rickets Dentin matrix protein 1 Nonsense mutation 



We are grateful to the family with ARHR for participation in our study. We thank Dr. Nobuaki Ito and Dr. Seiji Fukumoto of the University of Tokyo for the measurement of serum FGF23 levels and helpful comments.


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Copyright information

© The Japanese Society for Bone and Mineral Research and Springer 2010

Authors and Affiliations

  • Ryusuke Koshida
    • 1
  • Hideki Yamaguchi
    • 1
  • Koji Yamasaki
    • 1
  • Wakaba Tsuchimochi
    • 1
  • Tadato Yonekawa
    • 1
  • Masamitsu Nakazato
    • 1
  1. 1.Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Miyazaki Medical CollegeUniversity of MiyazakiMiyazakiJapan

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