{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T16:31:40Z","timestamp":1793291500152,"version":"4.5.0"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2010,4,7]],"date-time":"2010-04-07T00:00:00Z","timestamp":1270598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Homozygous inactivating mutations in DMP1 (dentin matrix protein 1), the gene encoding a noncollagenous bone matrix protein expressed in osteoblasts and osteocytes, cause autosomal recessive hypophosphatemia (ARHP). Herein we describe a family with ARHP owing to a novel homozygous DMP1 mutation and provide a detailed description of the associated skeletal dysplasia and carrier phenotype. The two adult patients with ARHP, a 78-year-old man and his 66-year-old sister, have suffered from bone pain and lower extremity varus deformities since early childhood. With increasing age, both patients developed severe joint pain, contractures, and complete immobilization of the spine. Radiographs showed short and deformed long bones, significant cranial hyperostosis, enthesopathies, and calcifications of the paraspinal ligaments. Biochemistries were consistent with hypophosphatemia owing to renal phosphate wasting; markers of bone turnover and serum fibroblast growth factor 23 (FGF-23) levels were increased significantly. Nucleotide sequence analysis of DMP1 revealed a novel homozygous mutation at the splice acceptor junction of exon 6 (IVS5-1G\u2009&amp;gt;\u2009A). Two heterozygous carriers of the mutation also showed mild hypophosphatemia, and bone biopsy in one of these individuals showed focal areas of osteomalacia. In bone, DMP1 expression was absent in the homozygote but normal in the heterozygote, whereas FGF-23 expression was increased in both subjects but higher in the ARHP patient. The clinical and laboratory observations in this family confirm that DMP1 has an important role in normal skeletal development and mineral homeostasis. The skeletal phenotype in ARHP may be significantly more severe than in other forms of hypophosphatemic rickets. \u00a9 2010 American Society for Bone and Mineral Research.<\/jats:p>","DOI":"10.1002\/jbmr.105","type":"journal-article","created":{"date-parts":[[2010,4,7]],"date-time":"2010-04-07T16:13:50Z","timestamp":1270656830000},"page":"2165-2174","source":"Crossref","is-referenced-by-count":54,"title":["Long-term clinical outcome and carrier phenotype in autosomal recessive hypophosphatemia caused by a novel <i>DMP1<\/i> mutation"],"prefix":"10.1093","volume":"25","author":[{"given":"Outi","family":"M\u00e4kitie","sequence":"first","affiliation":[{"name":"Folkh\u00e4lsan Institute of Genetics, Biomedicum Helsinki, Helsinki, Finland"},{"name":"Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata C","family":"Pereira","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilkka","family":"Kaitila","sequence":"additional","affiliation":[{"name":"Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serap","family":"Turan","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murat","family":"Bastepe","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tero","family":"Laine","sequence":"additional","affiliation":[{"name":"Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heikki","family":"Kr\u00f6ger","sequence":"additional","affiliation":[{"name":"Department of Surgery, Bone and Cartilage Research Unit, Kuopio University Hospital, Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William G","family":"Cole","sequence":"additional","affiliation":[{"name":"Division of Orthopaedic Surgery, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"J\u00fcppner","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 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