A novel nonsense mutation in the DMP1 gene in a Japanese family with autosomal recessive hypophosphatemic rickets
Autor: | Hideki Yamaguchi, Koji Yamasaki, Ryusuke Koshida, Wakaba Tsuchimochi, Tadato Yonekawa, Masamitsu Nakazato |
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Rok vydání: | 2010 |
Předmět: |
Male
medicine.medical_specialty Endocrinology Diabetes and Metabolism DNA Mutational Analysis Nonsense mutation Parathyroid hormone Genes Recessive medicine.disease_cause Short stature Endocrinology Asian People stomatognathic system Internal medicine medicine Humans Orthopedics and Sports Medicine Genetics Extracellular Matrix Proteins Mutation Base Sequence business.industry General Medicine Middle Aged Phosphoproteins medicine.disease DMP1 Pedigree Radiography Hypophosphatemic Rickets Codon Nonsense Female Familial Hypophosphatemic Rickets medicine.symptom business Renal phosphate excretion Hypophosphatemia |
Zdroj: | Journal of Bone and Mineral Metabolism. 28:585-590 |
ISSN: | 1435-5604 0914-8779 |
Popis: | 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)(2)D. 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 (98GA, 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. |
Databáze: | OpenAIRE |
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