title: A novel nonsense mutation in the DMP1 gene in a Japanese family with autosomal recessive hypophosphatemic rickets.
abstract: 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 (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.
authors.affiliation: Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Miyazaki Medical College, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Koshida
authors.forename: Hideki
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: Koji
authors.initials: K
authors.lastname: Yamasaki
authors.forename: Wakaba
authors.initials: W
authors.lastname: Tsuchimochi
authors.forename: Tadato
authors.initials: T
authors.lastname: Yonekawa
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Nakazato
mesh_terms: D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D053098:Familial Hypophosphatemic Rickets / Q000000981:diagnostic imaging / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010750:Phosphoproteins / Q000235:genetics*; D011859:Radiography
chemical_list: D018389:Codon, Nonsense; C513309:DMP1 protein, human; D016326:Extracellular Matrix Proteins; D010750:Phosphoproteins