Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0005940 (bone disease)
 7,459 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Osteogenesis imperfecta (OI) is a rare heritable bone disorder characterized by low bone mineral density (BMD), recurrent bone fractures, and progressive bone deformities. P4HB encodes protein disulfide isomerase (PDI) and is identified as a novel candidate gene of OI. The purposes of the present study are to detect pathogenic mutation, to evaluate the phenotypes of a Chinese family with mild OI, and to investigate the effects of bisphosphonates on bone of the proband. We detected the pathogenic mutation by next generation sequencing and Sanger sequencing. Laboratory and radiological investigations were conducted to evaluate the phenotypes. The proband was a 12-year-old girl with low BMD, history of recurrent non-traumatic fractures, slight scoliosis, with bluish grey sclera and ligamentous laxity. Her father suffered from one fragility fracture and slight wedge changes of vertebras, with bluish grey sclera. We identified a novel heterozygous missense mutation (c.692A>C, p.His231Pro) in P4HB in the proband and her father. This mutation was predicted to affect the combination of PDI with type I procollagen and lead to the disorder of its triple helix formation. Bisphosphonates were effective in reducing bone resorption and increasing BMD of the proband with well tolerance. In conclusion, we identified a novel mutation in P4HB in a Chinese family with mild OI, which expanded the genotypic and phenotypic spectrum of OI. Bisphosphonates were effective to this extremely rare OI induced by P4HB mutation.
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PMID:A novel missense mutation in P4HB causes mild osteogenesis imperfecta. 3094 99

Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue. Biomarkers of bone turnover have been used for years in bone disease management, especially to determine response to treatment. They are substances found in biological fluids, produced during the bone remodelling process. Recently, new approaches for the detection of bone physiology and pathology biomarkers have been proposed, among which proteomics, with particular interest in osteoporosis. The objective of this manuscript is to review current knowledge on proteomics applied to osteoporosis in vivo. The analysis of the 14 studies published to date showed a range of proteins whose expression is altered in patients with osteoporosis. The relatively small number of papers depends mainly on high costs and technical limitations; due to the difficulty to collect osteoclasts, most of the studies performed proteomics on peripheral blood monocytes (PBMs), already accepted as an excellent osteoporosis cell model in vivo. Among the identified proteins, the most promising are represented by Gelsolin (GSN), Annexin A2 (ANXA2), and Prolyl 4-hydroxylase (P4HB). They have been related to bone mineral density (BMD), sometimes in apparent disagreement (some upregulated and others downregulated in patients with low BMD). Finally, worthy of mention is the application of proteomics in the emerging field of microvesicles (MVs); they are important messengers, widely present in body fluids, and have recently emerged as novel targets for the diagnosis of multiple diseases, among which musculoskeletal diseases. In conclusion, the proteomic field is relatively novel in osteoporosis and has a considerable but theoretical potential; further investigations are needed in order to make proteome-derived markers applicable to clinical practice.
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PMID:Protein Markers in Osteoporosis. 3233 93