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《Endocrine practice》2013,19(5):e115-e117
ObjectiveTo report an unusual case of subungual exostosis in a patient on teriparatide.MethodsWe describe the presentation and symptoms of the patient and review of the relevant literature.ResultsTeriparatide is used for the treatment of osteoporosis. Rat studies using 3-60x the approved human dose have shown an association between teriparatide and an increased risk of osteosarcoma. Subungual exostosis, to our knowledge, has not been reported. We report the case of a 54-year-old female who presented with a 4-month history of pain and swelling in the medial side of her right thumb with no preceding trauma. The patient had history of severe osteoporosis with multiple fractures and was on teriparatide for 16 months. On examination, the right thumb was swollen and tender with no superficial erythema or signs of an infection. X-ray imaging revealed a trabecular bony overgrowth consistent with subungual exostosis. The patient was treated with subungual excision. Pathology showed endochondral bone formation with reactive atypia, consistent with osteocartilaginous exostosis.ConclusionTo our knowledge, this is the first case hypothesizing an association between teriparatide and subungual exostosis. Subungual exostosis is a benign growth of bone that arises in the distal phalanx, under or adjacent to the nail bed. The pathophysiology is not clearly understood, but the lesion has base of trabecular bone with a proliferating fibrocartilaginous cap. Teriparatide can stimulate the trabecular bone formation. Hence, an association between the use of teriparatide and the development of subungal exostosis cannot be excluded. Further studies delineating this relationship are needed. (Endocr. Pract. 2013;19:e115-e117) 相似文献
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The structural polymeric collagen of the skin of 19 patients with osteogenesis imperfecta has been examined. In those with severe bone disease, who often have white sclerae, this collagen fraction is less resistant to depolymerization than that of age-matched controls, though the total amount is normal. In patients with less severe bone disease, whose sclerae are usually blue, the polymeric collagen may have normal stability but the total amount is reduced. These results suggest defective cross-linking of collagen in severe osteogenesis imperfecta. 相似文献
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G. Orsini A. Majorana A. Mazzoni A. Putignano M. Falconi A. Polimeni L. Breschi 《European journal of histochemistry : EJH》2014,58(4)
Dentinogenesis imperfecta determines structural alterations of the collagen structure still not completely elucidated. Immunohisto-chemical analysis was used to assay type I and VI collagen, various non-collagenous proteins distribution in human primary teeth from healthy patients or from patients affected by type I dentinogenesis imperfecta (DGI-I) associated with osteogenesis imperfecta (OI). In sound primary teeth, an organized well-known ordered pattern of the type I collagen fibrils was found, whereas atypical and disorganized fibrillar structures were observed in dentin of DGI-I affected patients. Expression of type I collagen was observed in both normal and affected primary teeth, although normal dentin stained more uniformly than DGI-I affected dentin. Reactivity of type VI collagen was significantly lower in normal teeth than in dentin from DGI-I affected patients (P<0.05). Expressions of dentin matrix protein-1 (DMP1) and osteopontin (OPN) were observed in both normal dentin and dentin from DGI-I affected patients, without significant differences, being DMP1 generally more abundantly expressed. Immuno labeling for chondroitin sulfate (CS) and biglycan (BGN) was weaker in dentin from DGI-I-affected patients compared to normal dentin, this decrease being significant only for CS. This study shows ultra-structural alterations in dentin obtained from patients affected by DGI-I, supported by immunocytochemical assays of different collagenous and non-collagenous proteins.Key words: Osteogenesis imperfecta, dentinogenesis imperfecta, immuno-electron microscopy, collagen, non-collagenous proteins 相似文献
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Jae Won Choi Shari L. Sutor Lonn Lindquist Glenda L. Evans Benjamin J. Madden H. Robert Bergen III Theresa E. Hefferan Michael J. Yaszemski Richard J. Bram 《PLoS genetics》2009,5(12)
Osteogenesis Imperfecta (OI) is a human syndrome characterized by exquisitely fragile bones due to osteoporosis. The majority of autosomal dominant OI cases result from point or splice site mutations in the type I collagen genes, which are thought to lead to aberrant osteoid within developing bones. OI also occurs in humans with homozygous mutations in Prolyl-3-Hydroxylase-1 (LEPRE1). Although P3H1 is known to hydroxylate a single residue (pro-986) in type I collagen chains, it is unclear how this modification acts to facilitate collagen fibril formation. P3H1 exists in a complex with CRTAP and the peptidyl-prolyl isomerase cyclophilin B (CypB), encoded by the Ppib gene. Mutations in CRTAP cause OI in mice and humans, through an unknown mechanism, while the role of CypB in this complex has been a complete mystery. To study the role of mammalian CypB, we generated mice lacking this protein. Early in life, Ppib-/- mice developed kyphosis and severe osteoporosis. Collagen fibrils in Ppib-/- mice had abnormal morphology, further consistent with an OI phenotype. In vitro studies revealed that in CypB–deficient fibroblasts, procollagen did not localize properly to the golgi. We found that levels of P3H1 were substantially reduced in Ppib-/- cells, while CRTAP was unaffected by loss of CypB. Conversely, knockdown of either P3H1 or CRTAP did not affect cellular levels of CypB, but prevented its interaction with collagen in vitro. Furthermore, knockdown of CRTAP also caused depletion of cellular P3H1. Consistent with these changes, post translational prolyl-3-hydroxylation of type I collagen by P3H1 was essentially absent in CypB–deficient cells and tissues from CypB–knockout mice. These data provide significant new mechanistic insight into the pathophysiology of OI and reveal how the members of the P3H1/CRTAP/CypB complex interact to direct proper formation of collagen and bone. 相似文献
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Roberto Mendoza-Londono Somayyeh Fahiminiya Jacek Majewski CareRare Canada Consortium Martine Tétreault Javad Nadaf Peter Kannu Etienne Sochett Andrew Howard Jennifer Stimec Lucie Dupuis Paul Roschger Klaus Klaushofer Telma Palomo Jean Ouellet Hadil Al-Jallad John?S. Mort Pierre Moffatt Sergei Boudko Hans-Peter B?chinger Frank Rauch 《American journal of human genetics》2015,96(6):979-985
Secreted protein, acidic, cysteine-rich (SPARC) is a glycoprotein that binds to collagen type I and other proteins in the extracellular matrix. Using whole-exome sequencing to identify the molecular defect in two unrelated girls with severe bone fragility and a clinical diagnosis of osteogenesis imperfecta type IV, we identified two homozygous variants in SPARC (GenBank: ; c.497G>A [p.Arg166His] in individual 1; c.787G>A [p.Glu263Lys] in individual 2). Published modeling and site-directed mutagenesis studies had previously shown that the residues substituted by these mutations form an intramolecular salt bridge in SPARC and are essential for the binding of SPARC to collagen type I. The amount of SPARC secreted by skin fibroblasts was reduced in individual 1 but appeared normal in individual 2. The migration of collagen type I alpha chains produced by these fibroblasts was mildly delayed on SDS-PAGE gel, suggesting some overmodification of collagen during triple helical formation. Pulse-chase experiments showed that collagen type I secretion was mildly delayed in skin fibroblasts from both individuals. Analysis of an iliac bone sample from individual 2 showed that trabecular bone was hypermineralized on the material level. In conclusion, these observations show that homozygous mutations in SPARC can give rise to severe bone fragility in humans. NM_003118.3相似文献
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Cord Drgemüller Doreen Becker Adrian Brunner Bianca Haase Patrick Kircher Frank Seeliger Michael Fehr Ulrich Baumann Kerstin Lindblad-Toh Tosso Leeb 《PLoS genetics》2009,5(7)
Osteogenesis imperfecta (OI) is a hereditary disease occurring in humans and dogs. It is characterized by extremely fragile bones and teeth. Most human and some canine OI cases are caused by mutations in the COL1A1 and COL1A2 genes encoding the subunits of collagen I. Recently, mutations in the CRTAP and LEPRE1 genes were found to cause some rare forms of human OI. Many OI cases exist where the causative mutation has not yet been found. We investigated Dachshunds with an autosomal recessive form of OI. Genotyping only five affected dogs on the 50 k canine SNP chip allowed us to localize the causative mutation to a 5.82 Mb interval on chromosome 21 by homozygosity mapping. Haplotype analysis of five additional carriers narrowed the interval further down to 4.74 Mb. The SERPINH1 gene is located within this interval and encodes an essential chaperone involved in the correct folding of the collagen triple helix. Therefore, we considered SERPINH1 a positional and functional candidate gene and performed mutation analysis in affected and control Dachshunds. A missense mutation (c.977C>T, p.L326P) located in an evolutionary conserved domain was perfectly associated with the OI phenotype. We thus have identified a candidate causative mutation for OI in Dachshunds and identified a fifth OI gene. 相似文献
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《Endocrine practice》2014,20(7):e119-e122
ObjectiveThe leading signs and symptoms of Cushing’s syndrome (CS) in adolescents, which depend on the duration and the severity of hypercortisolemia, are: a decrease in growth velocity with an increase in body weight, redistribution of fat tissue (round face), and less commonly, acne due to hyperandrogenization. A widely used antiacne drug, retinoic acid, can change the clinical presentation of CS and delay the diagnosis.MethodsWe report an atypical presentation of adrenocorticotropic hormone (ACTH)-dependent CS in a patient treated with retinoic acid due to severe acne.ResultsThree months after the discontinuation of retinoic acid treatment (at a dose of 40 mg daily for 6 months, with a 4 month break and then for an additional 6 months), a 17.5-year-old male presented with short stature (− 3.0 SD), muscle weakness, difficulty concentrating, insomnia, and depressed mood. Body weight (body mass index, 22 kg/m2), fat tissue distribution, pubertal status (testicular volume equal to 20 mL, pubarche V, axillarche present), and blood pressure were normal, and the patient’s bone age was equal to his chronologic age. His bone mineral density was decreased (Z-score, − 3.5 SD). The morning serum cortisol level was normal (8:00 am, 171.9 ng/mL) and did not decrease in the evening (8:00 pm, 178.9 ng/mL) or after 1 mg of dexamethasone (100.4 ng/mL). The patient’s urinary free cortisol was elevated on 3 occasions (274.5, 217.3, and 253.7 μg/day). Increased ACTH levels in the morning (97.5 to 141.1 pg/mL) and postcorticoliberine (577.6 pg/mL) pointed to ACTH-dependent CS. A magnetic resonance imaging scan of the pituitary gland confirmed the presence of a microadenoma.ConclusionRetinoic acid treatment may alter the clinical presentation of ACTH-dependent CS and consequently delay the diagnosis. (Endocr Pract. 2014;20:e119-e122) 相似文献
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Osteogenesis imperfecta (OI) type V is an autosomal-dominant disease characterized by calcification of the forearm interosseous membrane, radial head dislocation, a subphyseal metaphyseal radiodense line, and hyperplastic callus formation. The causative mutation, c.-14C>T in the 5''-untranslated region of IFITM5, was recently discovered to be involved in this disease. However, in spite of the little genotypic variability, considerable phenotypic variability has been recognized in two cohorts of patients, the majority of whom were Caucasians. Using exome sequencing, we identified the same heterozygous mutation in four Chinese families with OI type V. This study confirms the molecular cause of OI type V and describes the phenotype of Chinese patients with this disorder. In conclusion, the phenotype of Chinese patients was generally similar to that of Caucasian patients. 相似文献
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《Endocrine practice》2022,28(10):1072-1077
ObjectiveTo summarize all available data using systematic review and meta-analysis to estimate the 1-year mortality risk after atypical femoral fracture (AFF) and risk ratio of mortality after AFF versus typical femoral fracture (TFF).MethodsPotentially eligible studies were identified from MEDLINE and Embase databases from inception to February 2022 using a search strategy that comprised the terms for “atypical femoral fracture” and “mortality.” An eligible study must consist of a cohort of patients with AFF. Then, the study must report the 1-year mortality rate after the AFF or report effect estimates with 95% confidence intervals, comparing the incident mortality between patients with AFF and TFF. Point estimates with standard errors were retrieved from each study and combined using the generic inverse variance method.ResultsA total of 8967 articles were identified. After 2 rounds of independent review by 3 investigators, we identified 7 studies reporting the 1-year mortality rate of AFFs and 3 studies comparing the mortality rate of AFF with that of TFF. Pooled analysis revealed a pooled 1-year mortality rate after an AFF of 0.10 (95% confidence interval, 0.05-0.16; I2 = 93.3%). Two studies compared the mortality risks of AFF with those of TFF and revealed conflicting results.ConclusionThe 1-year mortality rate after an AFF was approximately 10%. However, evidence is insufficient to conclude whether there was a difference in mortality risk between AFF and TFF. 相似文献
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Shang-Yi Lin Po-Liang Lu Kun-Bow Tsai Chun-Yu Lin Wei-Ru Lin Tun-Chieh Chen Ya-Ting Chang Chung-Hao Huang Chi-Yu Chen Chung-Chih Lai Yen-Hsu Chen 《Mycopathologia》2012,174(5-6):499-504
Mucormycosis is an invasive fungal infection associated with a high mortality rate, especially in immunocompromised hosts. Mucormycosis rarely occurs in cirrhotic patients. Here, we report a case of mucormycosis with underlying liver cirrhosis and diabetes mellitus. The patient suffered from maxillary sinusitis and osteomyelitis, and the infection was successfully treated with antifungal agents, surgical debridement, and hyperbaric oxygen therapy. The antifungal treatments used were liposomal amphotericin B, itraconazole, and posaconazole. Although our patient had liver cirrhosis (Child-Pugh classification B), no hepatic decompensation was developed during the treatment course of posaconazole. This is the first report of the safe and effective use of posaconazole for the treatment of mucormycosis in a cirrhotic patient. 相似文献
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Alfonso Gautieri Sebastien Uzel Simone Vesentini Markus J. Buehler 《Biophysical journal》2009,97(3):857-865
Osteogenesis imperfecta (OI) is a genetic disorder in collagen characterized by mechanically weakened tendon, fragile bones, skeletal deformities, and in severe cases, prenatal death. Although many studies have attempted to associate specific mutation types with phenotypic severity, the molecular and mesoscale mechanisms by which a single point mutation influences the mechanical behavior of tissues at multiple length scales remain unknown. We show by a hierarchy of full atomistic and mesoscale simulation that OI mutations severely compromise the mechanical properties of collagenous tissues at multiple scales, from single molecules to collagen fibrils. Mutations that lead to the most severe OI phenotype correlate with the strongest effects, leading to weakened intermolecular adhesion, increased intermolecular spacing, reduced stiffness, as well as a reduced failure strength of collagen fibrils. We find that these molecular-level changes lead to an alteration of the stress distribution in mutated collagen fibrils, causing the formation of stress concentrations that induce material failure via intermolecular slip. We believe that our findings provide insight into the microscopic mechanisms of this disease and lead to explanations of characteristic OI tissue features such as reduced mechanical strength and a lower cross-link density. Our study explains how single point mutations can control the breakdown of tissue at much larger length scales, a question of great relevance for a broad class of genetic diseases. 相似文献
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一成骨不全家系的COL1A1基因突变检测 总被引:7,自引:0,他引:7
成骨不全(Osteogenesisimperfecta,OI)是一种由于Ⅰ型胶原形成障碍,导致骨脆性增强为主要症状的 常染色体显性遗传性疾病。临床上主要表现为骨质脆弱、蓝巩膜、耳聋和中等程度的关节畸形等症状。成骨不全 基因分别定位于17q21.31 q22和7q22.1,其致病基因分别为COL1A1和COL1A2。对一常染色体显性遗传的 成骨不全家系进行连锁分析,在COL1A1遗传位点发现紧密连锁(LOD=9.31;θ=.00)。突变检测发现在 COL1A1基因第26内含子5′端剪接位点处存在一由GT转换为AT的致病突变,该突变引起的异常剪接是导致成 骨不全的致病原因之一。 相似文献
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Semler O Netzer C Hoyer-Kuhn H Becker J Eysel P Schoenau E 《Journal of musculoskeletal & neuronal interactions》2012,12(3):183-188
Osteogenesis imperfecta (OI) is a genetically heterogeneous disease leading to bone fragility. OI-VI is an autosomal-recessive form caused by mutations in SERPINF1. There is experimental evidence suggesting that loss of functional SERPINF1 leads to an activation of osteoclasts via the RANK/RANKL pathway. Patients with OI-VI show a poor response to bisphosphonates. We report on four children with OI-VI who had shown continuously elevated urinary bone resorption markers during a previous treatment with bisphosphonates. We treated these children with the RANKL antibody denosumab to reduce bone resorption. Intervention and results: Denosumab (1 mg/kg body weight) was injected s.c. every 3 months. There were no severe side effects. Markers of bone resorption decreased to the normal range after each injection. N-terminal Propeptide of collagen 1 was measured in the serum during the first treatment cycle and decreased also. Urinary deoxypyridinoline/creatinine was monitored in a total of seven treatment cycles and indicated that bone resorption reached the pre-treatment level after 6-8 weeks. Conclusion: This was the first use of denosumab in children with OI-VI. Denosumab was well tolerated, and laboratory parameters provided evidence that the treatment reversibly reduced bone resorption. Therefore, denosumab may be a new therapeutic option for patients with OI-VI. 相似文献