Long-term clinical outcome and carrier phenotype in autosomal recessive hypophosphatemia caused by a novel DMP1 mutation.
Long-term clinical outcome and carrier phenotype in autosomal recessive hypophosphatemia caused by a novel DMP1 mutation.
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DOI：
10.1002/jbmr.105
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发表时间：
2010-10
影响因子：
6.2
通讯作者：
Jueppner, Harald
中科院分区：
文献类型：
--
作者：
Makitie, Outi;Pereira, Renata C.;Kaitila, Ilkka;Turan, Serap;Bastepe, Murat;Laine, Tero;Kroger, Heikki;Cole, William G.;Jueppner, Harald
牙本质基质蛋白1（DMP 1）基因编码一种在成骨细胞和骨细胞中表达的非胶原性骨基质蛋白，其纯合失活突变可导致常染色体隐性低磷血症（ARHP）。在此，我们描述了一个家庭与ARHP由于一个新的纯合DMP 1突变，并提供了详细的描述相关的骨骼发育不良和载体表型。两名成人ARHP患者，一名78岁的男性和他66岁的妹妹，从童年早期就患有骨痛和下肢内翻畸形。随着年龄的增长，两名患者都出现了严重的关节疼痛、挛缩和脊柱完全固定。X线片显示长骨短且变形，显著的颅骨肥大，附着点病变和椎旁韧带钙化。由于肾性磷酸盐消耗，生物化学与低磷酸盐血症一致;骨转换标志物和血清成纤维细胞生长因子23（FGF-23）水平显著升高。核苷酸序列分析显示，DMP 1外显子6剪接受体连接处存在一个新的纯合突变（IVS 5 -1G > A）。两个突变的杂合子携带者也表现出轻度低磷血症，其中一个人的骨活检显示骨软化灶。在骨中，DMP 1表达在纯合子中不存在，但在杂合子中正常，而FGF-23表达在两个受试者中均增加，但在ARHP患者中更高。该家族的临床和实验室观察证实，DMP 1在正常骨骼发育和矿物质稳态中具有重要作用。ARHP的骨骼表型可能比其他形式的低磷血症性佝偻病更严重。© 2010美国骨与矿物质研究学会。
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 > A). 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. © 2010 American Society for Bone and Mineral Research.
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影响因子：
30.8
作者：
Lorenz-Depiereux, Bettina;Bastepe, Murat;Strom, Tim M.
通讯作者：
Strom, Tim M.
影响因子：
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Moura, Bertrand;Tubach, Florence;Le Parc, Jean-Marie
通讯作者：
Le Parc, Jean-Marie
影响因子：
4.8
作者：
Ye, L;Mishina, Y;Feng, JQ
通讯作者：
Feng, JQ