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Sample records for brtl osteogenesis imperfecta

  1. Sclerostin antibody improves skeletal parameters in a Brtl/+ mouse model of osteogenesis imperfecta.

    Science.gov (United States)

    Sinder, Benjamin P; Eddy, Mary M; Ominsky, Michael S; Caird, Michelle S; Marini, Joan C; Kozloff, Kenneth M

    2013-01-01

    Osteogenesis imperfecta (OI) is a genetic bone dysplasia characterized by osteopenia and easy susceptibility to fracture. Symptoms are most prominent during childhood. Although antiresorptive bisphosphonates have been widely used to treat pediatric OI, controlled trials show improved vertebral parameters but equivocal effects on long-bone fracture rates. New treatments for OI are needed to increase bone mass throughout the skeleton. Sclerostin antibody (Scl-Ab) therapy is potently anabolic in the skeleton by stimulating osteoblasts via the canonical wnt signaling pathway, and may be beneficial for treating OI. In this study, Scl-Ab therapy was investigated in mice heterozygous for a typical OI-causing Gly→Cys substitution in col1a1. Two weeks of Scl-Ab successfully stimulated osteoblast bone formation in a knock-in model for moderately severe OI (Brtl/+) and in WT mice, leading to improved bone mass and reduced long-bone fragility. Image-guided nanoindentation revealed no alteration in local tissue mineralization dynamics with Scl-Ab. These results contrast with previous findings of antiresorptive efficacy in OI both in mechanism and potency of effects on fragility. In conclusion, short-term Scl-Ab was successfully anabolic in osteoblasts harboring a typical OI-causing collagen mutation and represents a potential new therapy to improve bone mass and reduce fractures in pediatric OI.

  2. Rapidly growing Brtl/+ mouse model of osteogenesis imperfecta improves bone mass and strength with sclerostin antibody treatment.

    Science.gov (United States)

    Sinder, Benjamin P; Salemi, Joseph D; Ominsky, Michael S; Caird, Michelle S; Marini, Joan C; Kozloff, Kenneth M

    2015-02-01

    Osteogenesis imperfecta (OI) is a heritable collagen-related bone dysplasia, characterized by brittle bones with increased fracture risk that presents most severely in children. Anti-resorptive bisphosphonates are frequently used to treat pediatric OI and controlled clinical trials have shown that bisphosphonate therapy improves vertebral outcomes but has little benefit on long bone fracture rate. New treatments which increase bone mass throughout the pediatric OI skeleton would be beneficial. Sclerostin antibody (Scl-Ab) is a potential candidate anabolic therapy for pediatric OI and functions by stimulating osteoblastic bone formation via the canonical Wnt signaling pathway. To explore the effect of Scl-Ab on the rapidly growing OI skeleton, we treated rapidly growing 3week old Brtl/+ mice, harboring a typical heterozygous OI-causing Gly→Cys substitution on col1a1, for 5weeks with Scl-Ab. Scl-Ab had anabolic effects in Brtl/+ and led to new cortical bone formation and increased cortical bone mass. This anabolic action resulted in improved mechanical strength to WT Veh levels without altering the underlying brittle nature of the material. While Scl-Ab was anabolic in trabecular bone of the distal femur in both genotypes, the effect was less strong in these rapidly growing Brtl/+ mice compared to WT. In conclusion, Scl-Ab was able to stimulate bone formation in a rapidly growing Brtl/+ murine model of OI, and represents a potential new therapy to improve bone mass and reduce fracture risk in pediatric OI.

  3. Tissue level material composition and mechanical properties in Brtl/+ mouse model of Osteogenesis Imperfecta after sclerostin antibody treatment

    Science.gov (United States)

    Lloyd, William R.; Sinder, Benjamin P.; Salemi, Joseph; Ominsky, Michael S.; Marini, Joan C.; Caird, Michelle S.; Morris, Michael D.; Kozloff, Kenneth M.

    2015-02-01

    Osteogenesis imperfecta (OI) is a genetic disorder resulting in defective collagen or collagen-associated proteins and fragile, brittle bones. To date, therapies to improve OI bone mass, such as bisphosphonates, have increased bone mass in the axial skeleton of OI patients, but have shown limited effects at reducing long bone fragility. Sclerostin antibody (Scl- Ab), currently in clinical trials for osteoporosis, stimulates bone formation and may have the potential to reduce long bone fracture rates in OI patients. Scl-Ab has been investigated as an anabolic therapy for OI in the Brtl/+ mouse model of moderately severe Type IV OI. While Scl-Ab increases long bone mass in the Brtl/+ mouse, it is not known whether material properties and composition changes also occur. Here, we report on the effects of Scl-Ab on wild type and Brtl/+ young (3 week) and adult (6 month) male mice. Scl-Ab was administered over 5 weeks (25mg/kg, 2x/week). Raman microspectroscopy and nanoindentation are used for bone composition and biomechanical bone property measurements in excised bone. Fluorescent labels (calcein and alizarin) at 4 time points over the entire treatment period are used to enable measurements at specific tissue age. Differences between wild type and Brtl/+ groups included variations in the mineral and matrix lattices, particularly the phosphate v1, carbonate v1, and the v(CC) proline and hydroxyproline stretch vibrations. Results of Raman spectroscopy corresponded to nanoindentation findings which indicated that old bone (near midcortex) is stiffer (higher elastic modulus) than new bone. We compare and contrast mineral to matrix and carbonate to phosphate ratios in young and adult mice with and without treatment.

  4. Learning about Osteogenesis Imperfecta

    Science.gov (United States)

    ... genetic terms used on this page. Learning About Osteogenesis Imperfecta What is Osteogenesis imperfecta? What are the symptoms ... imperfecta Additional Resources on Osteogenesis imperfecta What is Osteogenesis imperfecta? Osteogenesis imperfecta (OI) is a genetic disorder that ...

  5. Osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Gupte Tejashri

    2006-05-01

    Full Text Available Osteogenesis imperfecta is an inherited disorder of the connective tissue. The extreme bone fragility seen in patients suffering from osteogenesis imperfecta pose a series of problems with regard to behavior management and rendering of quality dental treatment. Presented here a case of a four year old child suffering from osteogenesis imperfecta.

  6. What Is Osteogenesis Imperfecta?

    Science.gov (United States)

    ... your browser. Home Osteogenesis Imperfecta Osteogenesis Imperfecta Basics What Is Osteogenesis Imperfecta? Fast Facts: An Easy-to- ... Being Done on Osteogenesis Imperfecta? For More Information What Causes Osteogenesis Imperfecta? OI is caused by one ...

  7. Osteogenesis imperfecta.

    Science.gov (United States)

    Huber, Michaell A

    2007-03-01

    Osteogenesis imperfecta is a relatively common hereditary connective tissue disorder characterized by bone fragility and fractures. Other frequently affected tissues include tendons, ligaments, skin, sclera, teeth, and middle and inner ear. Molecular studies have demonstrated that most cases result from mutations affecting the genes responsible for the formation of type 1 collagen. The phenotypic presentation varies from mild to lethal. Commonly observed dental abnormalities include dentinogenesis imperfecta and malocclusion. Medical therapies using bisphosphonates have resulted in reduced fracture risk and decreased bone pain. To date, no cases of bisphosphonate-associated osteonecrosis have been reported. With appropriate precautions, the patient with osteogenesis imperfecta can tolerate and benefit from the delivery of necessary dental care to control oral disease, improve function, and improve esthetics.

  8. Osteogenesis imperfecta and dentinogenesis imperfecta: Associated disorders

    OpenAIRE

    2005-01-01

    This paper presents a review of dentinogenesis imperfecta occurring in patients with osteogenesis imperfecta. The systemic manifestations and the oral aspects of dentinogenesis imperfecta in osteogenesis imperfecta are discussed, and an illustrative case is described.

  9. Osteogenesis imperfecta and dentinogenesis imperfecta: associated disorders.

    Science.gov (United States)

    Rios, Daniela; Vieira, Ana Luiza Falavinha; Tenuta, Livia Maria Andaló; Machado, Maria Aparecida de Andrade Moreira

    2005-10-01

    This paper presents a review of dentinogenesis imperfecta occurring in patients with osteogenesis imperfecta. The systemic manifestations and the oral aspects of dentinogenesis imperfecta in osteogenesis imperfecta are discussed, and an illustrative case is described.

  10. Genetics Home Reference: osteogenesis imperfecta

    Science.gov (United States)

    ... Me Understand Genetics Home Health Conditions osteogenesis imperfecta osteogenesis imperfecta Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Osteogenesis imperfecta (OI) is a group of genetic disorders that ...

  11. Osteogenesis Imperfecta Overview

    Science.gov (United States)

    ... close(); docprint.focus(); */ } //--> Print-Friendly Page June 2015 Definition Osteogenesis imperfecta (OI) is a genetic disorder characterized ... OI lead productive and successful lives. They attend school, develop friendships and other relationships, have careers, raise ...

  12. Myths about OI (Osteogenesis Imperfecta)

    Science.gov (United States)

    ... Based on the OI Foundation publication Introduction to Osteogenesis Imperfecta: A Guide for Medical Professionals, Individuals and Families ... for Children, editor, 2013. Page updated August, 2015. © Osteogenesis Imperfecta Foundation, 2015 Privacy Policy

  13. What Are the Symptoms of Osteogenesis Imperfecta?

    Science.gov (United States)

    ... Resources and Publications What are the symptoms of osteogenesis imperfecta (OI)? Skip sharing on social media links Share ... decline and inability to breathe. 2 , 3 , 4 Osteogenesis Imperfecta Foundation. (2008). Respiratory issues in osteogenesis imperfecta. Retrieved ...

  14. Osteogenesis imperfecta type V

    DEFF Research Database (Denmark)

    Rauch, Frank; Moffatt, Pierre; Cheung, Moira;

    2013-01-01

    Osteogenesis imperfecta (OI) type V is an autosomal dominant bone fragility disorder that we had described a decade ago. Recent research has shown that OI type V is caused by a recurrent c.-14C>T mutation in IFITM5. In the present study, we assessed all patients diagnosed with OI type V at our...

  15. Child Abuse or Osteogenesis Imperfecta?

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    Child Abuse or Osteogenesis Imperfecta? 804 W. Diamond Ave., Ste. 210 Gaithersburg, MD 20878 (800) 981-2663 (301) ... welfare services to report a suspected case of child abuse. The child is taken away from the parents ...

  16. What Are the Treatments for Osteogenesis Imperfecta?

    Science.gov (United States)

    ... Resources and Publications What are the treatments for osteogenesis imperfecta (OI)? Skip sharing on social media links Share ... people with lung problems 4 Marini, J. (2010). Osteogenesis imperfecta. In F. Singer (Ed.), Diseases of bone and ...

  17. Osteogenesis imperfecta: cesarean deliveries in identical twins.

    Science.gov (United States)

    Dinges, E; Ortner, C; Bollag, L; Davies, J; Landau, R

    2015-02-01

    Osteogenesis imperfecta is a congenital disorder resulting in multiple fractures and extremely short stature, usually necessitating cesarean delivery. Identical twins with severe osteogenesis imperfecta each of whom underwent a cesarean delivery with different anesthetic modalities are presented. A review of the literature and anesthetic options for cesarean delivery and postoperative analgesia for women with osteogenesis imperfecta are discussed.

  18. Osteogenesis imperfecta/lobstein syndrome associated with dentinogenesis imperfecta.

    Science.gov (United States)

    Lingaraju, Naresh; Nagarathna, P J; Vijayalakshmi, R; Sheshadri, P

    2013-01-01

    Osteogenesis imperfecta is a collagen related disorder characterized by increased bone fragility and low bone mass. The important oral finding in osteogenesis imperfect is the presence of dentinogenesis imperfecta. This article presents a case of osteogenesis imperfecta (type IV B) with dentinogenesis imperfecta where a 7-year-old girl had opalacent primary teeth associated with severe bone deformity, scoliosis, barrel shaped rib cage, and short stature. The clinical, radiographic ad histologic features are reviewed along with management aspects.

  19. Metaphyseal bands in osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Suresh S

    2010-01-01

    Full Text Available An increasing number of patients with osteogenesis imperfecta are undergoing pamidronate therapy to prevent the incidence of fragility fractures. The authors herein report a child aged 3 years who received five cycles of pamidronate, resulting in metaphyseal bands, known as "zebra lines."

  20. The Spine in Patients With Osteogenesis Imperfecta.

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    Wallace, Maegen J; Kruse, Richard W; Shah, Suken A

    2017-02-01

    Osteogenesis imperfecta is a genetic disorder of type I collagen. Although multiple genotypes and phenotypes are associated with osteogenesis imperfecta, approximately 90% of the mutations are in the COL1A1 and COL1A2 genes. Osteogenesis imperfecta is characterized by bone fragility. Patients typically have multiple fractures or limb deformity; however, the spine can also be affected. Spinal manifestations include scoliosis, kyphosis, craniocervical junction abnormalities, and lumbosacral pathology. The incidence of lumbosacral spondylolysis and spondylolisthesis is higher in patients with osteogenesis imperfecta than in the general population. Use of diphosphonates has been found to decrease the rate of progression of scoliosis in patients with osteogenesis imperfecta. A lateral cervical radiograph is recommended in patients with this condition before age 6 years for surveillance of craniocervical junction abnormalities, such as basilar impression. Intraoperative and anesthetic considerations in patients with osteogenesis imperfecta include challenges related to fracture risk, airway management, pulmonary function, and blood loss.

  1. Dentinogenesis imperfecta associated with osteogenesis imperfecta

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    Mina Biria

    2012-01-01

    Full Text Available This paper presents a case with dentinogenesis imperfecta (DI associated with osteogenesis imperfecta. Systemic and dental manifestations of OI and its medical and dental treatments are discussed in this paper. A 5-year-old child with the diagnosis of OI was referred to the Dental School of Shaid Beheshti University of Medical Sciences. On clinical examination yellow/brown discoloration of primary teeth with the attrition of the exposed dentin and class III malocclusion was observed. Enamel of first permanent molars was hypoplastic. Radiographic examinations confirmed the diagnosis of DI. A histological study was performed on one of the exfoliating teeth, which showed abnormal dentin. Primary teeth with DI were more severely affected compared to permanent teeth; enamel disintegration occurred in teeth with DI, demonstrating the need for restricts recalls for these patients.

  2. Dentinogenesis imperfecta associated with osteogenesis imperfecta.

    Science.gov (United States)

    Biria, Mina; Abbas, Fatemeh Mashhadi; Mozaffar, Sedighe; Ahmadi, Rahil

    2012-07-01

    This paper presents a case with dentinogenesis imperfecta (DI) associated with osteogenesis imperfecta. Systemic and dental manifestations of OI and its medical and dental treatments are discussed in this paper. A 5-year-old child with the diagnosis of OI was referred to the Dental School of Shaid Beheshti University of Medical Sciences. On clinical examination yellow/brown discoloration of primary teeth with the attrition of the exposed dentin and class III malocclusion was observed. Enamel of first permanent molars was hypoplastic. Radiographic examinations confirmed the diagnosis of DI. A histological study was performed on one of the exfoliating teeth, which showed abnormal dentin. Primary teeth with DI were more severely affected compared to permanent teeth; enamel disintegration occurred in teeth with DI, demonstrating the need for restricts recalls for these patients.

  3. Osteogenesis imperfecta: pathophysiology and treatment.

    Science.gov (United States)

    Hoyer-Kuhn, Heike; Netzer, Christian; Semler, Oliver

    2015-07-01

    Osteogenesis imperfecta is a rare hereditary disease mostly caused by mutations impairing collagen synthesis and modification. Recently recessive forms have been described influencing differentiation and activity of osteoblasts and osteoclasts. Most prominent signs are fractures due to low traumata and deformities of long bones and vertebrae. Additional patients can be affected by dwarfism, scoliosis Dentinogenesis imperfecta, deafness and a blueish discoloration of the sclera. During childhood state of the art medical treatment are i.v. bisphosphonates to increase bone mass and to reduce fracture rate. Surgical interventions are needed to treat fractures, to correct deformities and should always be accompanied by physiotherapeutic and rehabilitative interventions.

  4. Treatment Concepts of Osteogenesis Imperfecta

    Directory of Open Access Journals (Sweden)

    Ramji Lal Sahu

    2012-06-01

    Full Text Available Background: To explore the Application of the intramedullary nails for correction of deformity in the lower limbs and decrease the opportunity of refractures in children with osteogenesis imperfecta.Materials and Methods: From July 2005 to July 2009, 11 patients (5 males and 6 females, were recruited from Emergency and outpatient department having deformities of osteogenesis imperfecta in lower limbs. With 3 femurs and 5 tibias with deformity in lower limps were corrected by multiosteotomy and fixed with intramedullary interlocking nails, 6 (3 femurs and 3 tibias for Rush nails; 6 (2 femurs and 4 tibias for Ender nails; and 12 (6 femurs and 6 tibias for flexible intramedullary nails. All patients were operated under general or spinal anesthesia. Results: All deformities were perfectly corrected. All patients were available at final follow up, for 9 months to 36 months, mean 18 months. 2 patients had delayed union, 2 had superficial infection in the incision or pin tract, and 1 had refractures postoperatively. The results were excellent in 72.727% and good in 27.272% patients. Conclusion: Multiosteotomy and fixed intramedullary nails can correct the deformity in the lower limbs perfectly and decrease the opportunity of refractures in children with osteogenesis imperfecta, which has been proved to be a reliable method.

  5. CT findings of osteogenesis imperfecta

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    Kojo, Nobuto; Otsuru, Katsuyasu; Lee, Soichi; Takagi, Shigeyuki; Shigemori, Minoru.

    1987-08-01

    Two cases of osteogenesis imperfecta found in one family (father and daughter) are reported, and the CT findings are described. Case 1 is a 58-year-old man who fell and struck his head at home on November 10, 1984. He was transferred to Omuta City Hospital when he became semicomatose and decerebrate posturing was noted. His family history revealed 8 persons with osteogenesis imperfecta. A skull X-ray film showed a large skull vault, many wormian bones at the lambdoid suture, platybasia, and a basilar impression. A CT scan demonstrated a right acute subdural hematoma, while the bone image showed well-developed mastoid air cells and a skull deformity characteristic of osteogenesis imperfecta. He had an emergency operation, and a 170-gr clot was successfully evacuated. A postoperative CT scan demonstrated brain atrophy, possibly present before head trauma. Case 2 is the daughter of Case 1 (a 27-year-old woman). She also showed characteristic neuroradiological manifestations on a plain skull film and on a CT scan. A basilar impression and platybasia were also demonstrated. In this report, the possible mechanism of the production of a traumatic acute subdural hematoma is also discussed.

  6. Osteogenesis Imperfecta Issues: Constipation

    Science.gov (United States)

    OI Issues: Constipation 804 W. Diamond Ave., Ste. 210 Gaithersburg, MD 20878 (800) 981-2663 (301) 947-0083 Fax: (301) 947- ... a cure, education, awareness, and mutual support. Introduction Constipation is a problem for some people with osteogenesis ...

  7. Bone tissue ultrastructural defects in a mouse model for osteogenesis imperfecta: a Raman spectroscopy study

    Science.gov (United States)

    Chen, Tsoching; Kozloff, Kenneth M.; Goldstein, Steven A.; Morris, Michael D.

    2004-07-01

    Osteogenesis imperfecta (OI) is genetic defect in which the genes that code for the α1(I) or α2(I) chains of type I collagen are defective. The defects often result in substitution of a bulky amino acid for glycine, causing formation of collagen that can not form the normal triple helix. Depending on the details of the defects, the outcomes range from controllable to lethal. This study focuses on OI type IV, a more common and moderately severe form of the disease. People with the disease have a substantial increase in the risk and rate of fracture. We examine the spectroscopic consequences of these defects, using a mouse model (BRTL) that mimics OI type IV. We compare Raman images from tibial cortical tissue of wild-type mice and BRTL mice with single copy of mutation and show that both mineral to matrix ratios and collagen inter-fibril cross-links are different in wild-type and mutant mice.

  8. Impaired osteoblastogenesis in a murine model of dominant osteogenesis imperfecta: a new target for osteogenesis imperfecta pharmacological therapy.

    Science.gov (United States)

    Gioia, Roberta; Panaroni, Cristina; Besio, Roberta; Palladini, Giovanni; Merlini, Giampaolo; Giansanti, Vincenzo; Scovassi, Ivana A; Villani, Simona; Villa, Isabella; Villa, Anna; Vezzoni, Paolo; Tenni, Ruggero; Rossi, Antonio; Marini, Joan C; Forlino, Antonella

    2012-07-01

    The molecular basis underlying the clinical phenotype in bone diseases is customarily associated with abnormal extracellular matrix structure and/or properties. More recently, cellular malfunction has been identified as a concomitant causative factor and increased attention has focused on stem cells differentiation. Classic osteogenesis imperfecta (OI) is a prototype for heritable bone dysplasias: it has dominant genetic transmission and is caused by mutations in the genes coding for collagen I, the most abundant protein in bone. Using the Brtl mouse, a well-characterized knockin model for moderately severe dominant OI, we demonstrated an impairment in the differentiation of bone marrow progenitor cells toward osteoblasts. In mutant mesenchymal stem cells (MSCs), the expression of early (Runx2 and Sp7) and late (Col1a1 and Ibsp) osteoblastic markers was significantly reduced with respect to wild type (WT). Conversely, mutant MSCs generated more colony-forming unit-adipocytes compared to WT, with more adipocytes per colony, and increased number and size of triglyceride drops per cell. Autophagy upregulation was also demonstrated in mutant adult MSCs differentiating toward osteogenic lineage as consequence of endoplasmic reticulum stress due to mutant collagen retention. Treatment of the Brtl mice with the proteasome inhibitor Bortezomib ameliorated both osteoblast differentiation in vitro and bone properties in vivo as demonstrated by colony-forming unit-osteoblasts assay and peripheral quantitative computed tomography analysis on long bones, respectively. This is the first report of impaired MSC differentiation to osteoblasts in OI, and it identifies a new potential target for the pharmacological treatment of the disorder.

  9. Osteogenesis imperfecta with joint contractures: Bruck syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Blacksin, M.F. [Department of Radiology, University of Medicine and Dentistry of New Jersey, 150 Bergen St., Rm. C320, Newark, NJ 07103-2426 (United States); Pletcher, B.A. [Center for Human and Molecular Genetics, Department of Pediatrics, University of Medicine and Dentistry of New Jersey, Newark, New Jersey (United States); David, M. [Department of Radiology, Newark-Beth Israel Medical Center, Newark, New Jersey (United States)

    1998-02-01

    We describe an Egyptian boy with osteogenesis imperfecta who was born with thumb contractures and bilateral antecubital pterygia. He was seen at 16 months of age with femur and tibial fractures, thoracic vertebral compression fractures, scoliosis and Wormian bones. The findings are consistent with a diagnosis of Bruck syndrome. (orig.) With 1 fig., 5 refs.

  10. Osteogenesis imperfecta in childhood : Prognosis for walking

    NARCIS (Netherlands)

    Engelbert, RHH; Uiterwaal, CSPM; Gulmans, VAM; Pruijs, H; Helders, PJM

    2000-01-01

    Objectives: We studied the predicted value of disease-related characteristics for the ability of children with osteogenesis imperfecta (OI) to walk. Study design: The severity of OI was classified according to Sillence. The parents were asked to report the age at which the child achieved motor miles

  11. Bone Material Properties in Osteogenesis Imperfecta.

    Science.gov (United States)

    Bishop, Nick

    2016-04-01

    Osteogenesis imperfecta entrains changes at every level in bone tissue, from the disorganization of the collagen molecules and mineral platelets within and between collagen fibrils to the macroarchitecture of the whole skeleton. Investigations using an array of sophisticated instruments at multiple scale levels have now determined many aspects of the effect of the disease on the material properties of bone tissue. The brittle nature of bone in osteogenesis imperfecta reflects both increased bone mineralization density-the quantity of mineral in relation to the quantity of matrix within a specific bone volume-and altered matrix-matrix and matrix mineral interactions. Contributions to fracture resistance at multiple scale lengths are discussed, comparing normal and brittle bone. Integrating the available information provides both a better understanding of the effect of current approaches to treatment-largely improved architecture and possibly some macroscale toughening-and indicates potential opportunities for alternative strategies that can influence fracture resistance at longer-length scales.

  12. Cardiovascular disease in patients with osteogenesis imperfecta

    DEFF Research Database (Denmark)

    Folkestad, Lars; Hald, Jannie Dahl; Gram, Jeppe

    2016-01-01

    BACKGROUND: Osteogenesis imperfecta (OI) is a hereditary connective tissue disease often due to mutations in genes coding for type 1 collagen. Collagen type 1 is important in the development of the heart and vasculature. Little is known about the risk of cardiovascular disease (CVD) in OI...... to development of these diseases. Our results suggest that the collagenopathy seen in OI may be part of the pathogenesis of CVD in OI....

  13. Dentinogenesis imperfecta associated with osteogenesis imperfecta: report of two cases.

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    Tsai, Chia-Ling; Lin, Yng-Tzer; Lin, Yai-Tin

    2003-02-01

    Osteogenesis imperfecta (OI) is a heritable systemic disorder of the connective tissue. Dentinogenesis imperfecta (DI), which is sometimes an accompanying symptom of OI, belongs to a group of genetically conditioned dentin dysplasias and is characterized clinically by an opalescent amber appearance of the dentin. Although the teeth of DI cases wear more easily and excessively compared to normal teeth, they do not appear to be more susceptible to dental caries than normal teeth. Two cases of DI associated with OI are presented in this paper, with 1 case suffering from nursing bottle caries. The purposes of this paper are to present the dental and skeletal characteristics of moderately and mildly involved DI associated with OI, and to discuss the possible methods of dental treatment. Patients with OI and opalescent teeth should be evaluated as soon as the deciduous teeth erupt; immediate dental involvement and oral hygiene instruction can be of help in reducing the necessity of extensive dental care.

  14. Osteogenesis Imperfecta, Pseudoachalasia, and Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Dilsa Mizrak

    2015-01-01

    Full Text Available Osteogenesis imperfecta (OI is a rare, inherited skeletal disorder characterized by abnormalities of type 1 collagen. Malignancy is rarely reported in patients with OI and it was suggested that this disease can protect against cancer. Here, we report a 41-year-old woman with symptoms of achalasia where repeated treatment of pneumatic dilation and stent replacement was unsuccessful; therefore, surgery was performed. Pathology showed gastric adenocarcinoma unexpectedly. Chemotherapy was given after assessing dihydropyrimidine dehydrogenase (DPD enzyme activity, which can be deficient in OI patients. This is the first report of gastric cancer mimicking achalasia in a patient with OI.

  15. A rare combination of amniotic constriction band with osteogenesis imperfecta.

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    Shah, Krupa Hitesh; Shah, Hitesh

    2015-11-11

    Amniotic constriction bands and osteogenesis imperfecta are disorders arising from a collagen defect. We report a rare association of amniotic bands with osteogenesis imperfecta in a child. The child was born with multiple amniotic bands involving the right leg, both hands and both feet. Multiple fractures of long bones of lower limbs occurred in childhood due to trivial trauma. Deformities of the femur and tibia due to malunion with osteopenia and blue sclerae were present. The patient was treated with z plasty of constriction band of the right tibia and bisphosphonate for osteogenesis imperfecta. This rare association of both collagen diseases may provide further insight for the pathogenesis of these diseases.

  16. Hyperplastic callus formation in osteogenesis imperfecta. A case report

    Energy Technology Data Exchange (ETDEWEB)

    Burchardt, A.J. (Depts. of Radiology and Pediatric Orthopedic Surgery, Rigshospitalet, Copenhagen Univ. (Denmark)); Wagner, A.A. (Depts. of Radiology and Pediatric Orthopedic Surgery, Rigshospitalet, Copenhagen Univ. (Denmark)); Basse, P. (Depts. of Radiology and Pediatric Orthopedic Surgery, Rigshospitalet, Copenhagen Univ. (Denmark))

    1994-09-01

    We report a case of bilateral hyperplastic callus formation as a complication of fracture in a patient with osteogenesis imperfecta. The clinical and radiographic findings and the differential diagnosis are discussed. (orig.).

  17. Osteogenesis Imperfecta:No Place for Imperfect Anaesthesiologist

    Directory of Open Access Journals (Sweden)

    Geeta Bhandari

    2008-01-01

    Full Text Available Osteogenesis imperfecta, an inherited disease of connective tissue, is associated with anatomic and physiologic abnormalities which make any form of anaesthesia a challenging task for the anaesthesiologist. We report a case of Osteogenesis imperfecta type -IV with severe anatomic deformities, who underwent replacement nailing procedure for periprosthetic fracture of shaft femur under general anaesthesia. We used a proseal LMA in the case, patient suffered a posterior dislocation of right shoulder on repositioning at the end of the surgery.

  18. The Relationship between Osteogenesis Imperfecta and Spinal Muscular Atrophy

    Directory of Open Access Journals (Sweden)

    Babak Soltani

    2011-09-01

    Full Text Available ObjectiveA 4-month-old female with osteogenesis imperfecta (OI type II was admitted in PICU of our center due to severe respiratory distress and fever with a diagnosis of severe pneumonia, and mechanical ventilation was initiated. Due to severe hypotonia, NCV and EMG were performed, and spinal muscular atrophy (SMA type I was diagnosed.Keywords: Osteogenesis imperfecta; spinal muscular atrophy; hypotonia

  19. Valvular and aortic diseases in osteogenesis imperfecta.

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    Lamanna, Arvin; Fayers, Trevor; Clarke, Sophie; Parsonage, William

    2013-10-01

    Osteogenesis imperfecta (OI) is an inheritable connective tissue disorder caused by defective collagen synthesis with the principal manifestations of bone fragility. OI has been associated with left sided valvular regurgitation and aortic dilation. Valve and aortic surgery are technically feasible in patients with OI but are inherently high risk due to the underlying connective tissue defect. This report reviews the valvular and aortic pathology associated with OI and their management. We describe two cases of patients with OI who have significant aortic and mitral valve regurgitation, one of whom has been managed conservatively and the other who has undergone successful mitral valve repair and aortic valve replacement. The latter case represents the fifth case of mitral valve repair in a patient with OI reported in the medical literature.

  20. IFITM5 mutations and osteogenesis imperfecta.

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    Hanagata, Nobutaka

    2016-03-01

    Interferon-induced transmembrane protein 5 (IFITM5) is an osteoblast-specific membrane protein that has been shown to be a positive regulatory factor for mineralization in vitro. However, Ifitm5 knockout mice do not exhibit serious bone abnormalities, and thus the function of IFITM5 in vivo remains unclear. Recently, a single point mutation (c.-14C>T) in the 5' untranslated region of IFITM5 was identified in patients with osteogenesis imperfecta type V (OI-V). Furthermore, a single point mutation (c.119C>T) in the coding region of IFITM5 was identified in OI patients with more severe symptoms than patients with OI-V. Although IFITM5 is not directly involved in the formation of bone in vivo, the reason why IFITM5 mutations cause OI remains a major mystery. In this review, the current state of knowledge of OI pathological mechanisms due to IFITM5 mutations will be reviewed.

  1. Assessment of dysplastic dentin in osteogenesis imperfecta and dentinogenesis imperfecta.

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    Malmgren, Barbro; Lindskog, Sven

    2003-04-01

    Two semiquantitative scoring systems, Clinical Radiographic Score (CRS) and Dysplastic Dentin Score (DDS), were introduced for analyzing degree of dysplastic manifestations in dentin. The utility of both systems was demonstrated in a large material of teeth from patients with dentinogenesis imperfecta (DI) and osteogenesis imperfecta (OI). Twenty teeth from healthy controls, 81 teeth from 40 patients with OI, and 18 teeth with DI without OI (DI type II) were examined. The degree of dysplasia was correlated with type and form of OI and type of DI. The median DDS did not differ between DI associated with OI (DI type I) and DI type II. DDS in OI patients without clinical signs of DI was above that of control teeth. Both circumpulpal and mantle dentin showed increased DDS, although circumpulpal dentin was more severely affected. The median DDS was highest for the most severe type of non-lethal OI (type III). DDS increased significantly with form (severity) of OI. A significant association between DDS and CRS was found, although diagnosis of DI in less severe cases was not possible based on radiographic or clinical signs alone. Thus, the DDS system proved valuable when the CRS system based on radiographic/clinical manifestations failed, the most significant finding being subclinical histological manifestations of DI in patients with OI but without clinical or radiographic signs of DI. These subtle dysplastic changes are most likely an expression of genetic disturbances associated with OI and should not be diagnosed as DI, but rather be termed histologic manifestations of dysplastic dentin associated with OI.

  2. Orthodontic and orthognathic management of a patient with osteogenesis imperfecta and dentinogenesis imperfecta: a case report.

    Science.gov (United States)

    Kindelan, J; Tobin, M; Roberts-Harry, D; Loukota, R A

    2003-12-01

    This case report describes a patient's severe Class III malocclusion, managed with a combination of orthodontic and orthognathic treatment. The medical history was complicated by osteogenesis imperfecta and dentinogenesis imperfecta. In addition the patient was a Jehovah's Witness. Patients with osteogenesis imperfecta carry an increased risk of perioperative haemorrhage, and this led to bimaxillary surgery being carried out as two discrete surgical episodes for the patient described. In addition, the risk of enamel fracture led to orthodontic bands being cemented on all teeth. In spite of the increased risks a successful outcome was achieved.

  3. Pseudomass of the sternal manubrium in osteogenesis imperfecta

    Energy Technology Data Exchange (ETDEWEB)

    Yekeler, Ensar; Kumbasar, Basak; Dursun, Memduh; Tunaci, Mehtap [Department of Radiology, Istanbul University, Istanbul Faculty of Medicine, 34390, Capa, Istanbul (Turkey); Cantez, Serdar; Emiroglu, Halil Haldun [Department of Pediatrics, Istanbul University, Istanbul Faculty of Medicine, 34390, Capa, Istanbul (Turkey)

    2003-06-01

    Skeletal abnormalities such as hypertrophic callus formation and ''popcorn'' calcifications are rare radiological findings of osteogenesis imperfecta, causing tumor-like appearances on imaging. We report on a 7-year-old girl with osteogenesis imperfecta presenting with hepatomegaly and palpable lymphadenopathy in the left inguinal region on physical examination. Computed tomography examination revealed a high-density mass-like lesion of the manubrium sterni. Ultrasonography and a lateral roentgenogram of the chest verified that this was a pseudomass caused by a bowed sternal manubrium. (orig.)

  4. Prenatal diagnosis of lethal osteogenesis imperfecta in twin pregnancy.

    Science.gov (United States)

    Morin, L R; Herlicoviez, M; Loisel, J C; Jacob, B; Feuilly, C; Stanescu, V

    1991-06-01

    Lethal osteogenesis imperfecta was diagnosed at 27 weeks amenorrea in one fetus of a bichorial twin pregnancy. Sonographic findings included: short-limb dwarfism, hypotrophy and hypoechoic bones. The affected fetus was so translucent that only the normal fetus could be seen on plain in utero radiography. The affected fetus died immediately after birth. Postmortem radiography and histology were typical of lethal osteogenesis imperfecta of type IIA. Aids to the etiological diagnosis of in utero dwarfism are presented. Sonographic features correlated with neonatal death are described.

  5. A CASE OF OSTEOGENESIS IMPERFECTA WITH S IGNIFICANT DISABILITY

    Directory of Open Access Journals (Sweden)

    Sahana

    2014-01-01

    Full Text Available Osteogenesis imperfecta (OI is a rare genetic disorder characterized by structural and quantitative defects in type 1 collagen resulting in susceptibility to fractures of long bones or vertebral compressions from mild or inconsequential trauma 1 .There are different types that range in seve rity from mild form to perinatal lethal form. We present a case of type 3 osteogenesis imperfect with multiple fractures , severe short stature and severe disability who survived till 5 years of age.

  6. Mortality and Causes of Death in Patients With Osteogenesis Imperfecta

    DEFF Research Database (Denmark)

    Folkestad, Lars; Hald, Jannie Dahl; Canudas-Romo, Vladimir;

    2016-01-01

    Osteogenesis imperfecta (OI) is a hereditary connective tissue disease that causes frequent fractures. Little is known about causes of death and length of survival in OI. The objective of this work was to calculate the risk and cause of death, and the median survival time in patients with OI...

  7. Fracture Rates and Fracture Sites in Patients With Osteogenesis Imperfecta

    DEFF Research Database (Denmark)

    Folkestad, Lars; Hald, Jannie Dahl; Ersbøll, Annette Kjær;

    2017-01-01

    Osteogenesis imperfecta (OI) is a hereditary, clinically heterogeneous, connective tissue disorder. The population prevalence of OI in Denmark is 10.6 in 100,000. A hallmark of the disease is frequent fractures that are often precipitated by minimal trauma. The aim of the current study...

  8. A rare case of Osteogenesis Imperfecta Type III

    Directory of Open Access Journals (Sweden)

    Nagaraj MV, Jehangir HM

    2014-03-01

    Full Text Available Osteogenesis imperfecta (OI the most common genetic cause of osteoporosis is a generalized disorder of connective tissue, characterized by increased bone fragility, low bone mass, recurrent fractures & numerous extra-osseous features with unusual presentations. We report a case of 7 year old female child presenting with respiratory distress with bowing of limb. This case is presented for its rarity.

  9. Wormian bones in osteogenesis imperfecta and other disorders

    Energy Technology Data Exchange (ETDEWEB)

    Cremin, B.; Goodman, H.; Spranger, J.; Beighton, P.

    1982-03-01

    When are Wormian bones significant is not an easy question to answer, but its relevance is important in relation to bone dysplasias such as osteogenesis imperfecta. Recognition will differ with age of patient, radiographic objectivity, and personal subjectivity. In order to attempt an answer, the skull radiographs of 81 cases of osteogenesis imperfecta of varying ages were examined for the presence of Wormian bones. These were compared against the incidence of Wormian bones in 500 skull radiographs of normal children. Significant Wormian bones as against normal developmental variants were considered to be those more than 10 in number, measuring greater than 6 mm by 4 mm, and arranged in a general mosaic pattern. They were found in all the cases of osteogenesis imperfecta but not in the normal skulls. The occurrence of significant Wormian bones in other bone dysplasias from our material and that of the literature was recorded. Other incidental findings in the skulls of the cases of osteogenesis imperfecta were also appraised.

  10. Complete COL1A1 allele deletions in osteogenesis imperfecta

    NARCIS (Netherlands)

    van Dijk, Fleur S.; Huizer, Margriet; Kariminejad, Ariana; Marcelis, Carlo L.; Plomp, Astrid S.; Terhal, Paulien A.; Meijers-Heijboer, Hanne; Weiss, Marjan M.; van Rijn, Rick R.; Cobben, Jan M.; Pals, Gerard

    2010-01-01

    Purpose: To identify a molecular genetic cause in patients with a clinical diagnosis of osteogenesis imperfecta (OI) type I/IV. Methods: The authors performed multiplex ligation-dependent probe amplification analysis of the COL1A1 gene in a group of 106 index patients. Results: In four families with

  11. The Relationship between Osteogenesis Imperfecta and Spinal Muscular Atrophy

    Directory of Open Access Journals (Sweden)

    Babak Soltani

    2011-06-01

    Full Text Available ObjectiveA 4-month-old female with osteogenesis imperfecta (OI type II was admitted in PICU of our center due to severe respiratory distress and fever with a diagnosis of severe pneumonia, and mechanical ventilation was initiated. Due to severe hypotonia, NCV and EMG were performed, and spinal muscular atrophy (SMA type I was diagnosed.

  12. Collagen-derived markers of bone metabolism in osteogenesis imperfecta

    DEFF Research Database (Denmark)

    Lund, A M; Hansen, M; Kollerup, Gina Birgitte;

    1998-01-01

    )] were measured in 78 osteogenesis imperfecta (OI) patients to investigate bone metabolism in vivo and relate marker concentrations to phenotype and in vitro collagen I defects, as shown by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). PICP and PINP were generally low...

  13. Osteogenesis imperfecta: the audiological phenotype lacks correlation with the genotype.

    NARCIS (Netherlands)

    Swinnen, F.K.R.; Coucke, P.J.; Paepe, A.M. De; Symoens, S.; Malfait, F.; Gentile, F.V.; Sangiorgi, L.; D'Eufemia, P.; Celli, M.; Garretsen, T.J.; Cremers, C.W.R.J.; Dhooge, I.J.; Leenheer, E. de

    2011-01-01

    ABSTRACT: BACKGROUND: Osteogenesis Imperfecta (OI) is a heritable connective tissue disorder mainly caused by mutations in the genes COL1A1 and COL1A2 and is associated with hearing loss in approximately half of the cases. The hearing impairment usually starts between the second and fourth decade of

  14. Effect of anti-sclerostin therapy and osteogenesis imperfecta on tissue-level properties in growing and adult mice while controlling for tissue age.

    Science.gov (United States)

    Sinder, Benjamin P; Lloyd, William R; Salemi, Joseph D; Marini, Joan C; Caird, Michelle S; Morris, Michael D; Kozloff, Kenneth M

    2016-03-01

    Bone composition and biomechanics at the tissue-level are important contributors to whole bone strength. Sclerostin antibody (Scl-Ab) is a candidate anabolic therapy for the treatment of osteoporosis that increases bone formation, bone mass, and bone strength in animal studies, but its effect on bone quality at the tissue-level has received little attention. Pre-clinical studies of Scl-Ab have recently expanded to include diseases with altered collagen and material properties such as osteogenesis imperfecta (OI). The purpose of this study was to investigate the role of Scl-Ab on bone quality by determining bone material composition and tissue-level mechanical properties in normal wild type (WT) tissue, as well as mice with a typical OI Gly➔Cys mutation (Brtl/+) in type I collagen. Rapidly growing (3-week-old) and adult (6-month-old) WT and Brtl/+ mice were treated for 5weeks with Scl-Ab. Fluorescent guided tissue-level bone composition analysis (Raman spectroscopy) and biomechanical testing (nanoindentation) were performed at multiple tissue ages. Scl-Ab increased mineral to matrix in adult WT and Brtl/+ at tissue ages of 2-4wks. However, no treatment related changes were observed in mineral to matrix levels at mid-cortex, and elastic modulus was not altered by Scl-Ab at any tissue age. Increased mineral-to-matrix was phenotypically observed in adult Brtl/+ OI mice (at tissue ages>3wks) and rapidly growing Brtl/+ (at tissue ages>4wks) mice compared to WT. At identical tissue ages defined by fluorescent labels, adult mice had generally lower mineral to matrix ratios and a greater elastic modulus than rapidly growing mice, demonstrating that bone matrix quality can be influenced by animal age and tissue age alike. In summary, these data suggest that Scl-Ab alters the matrix chemistry of newly formed bone while not affecting the elastic modulus, induces similar changes between Brtl/+ and WT mice, and provides new insight into the interaction between tissue age and

  15. A Guide to Education for Children with Osteogenesis Imperfecta. What Is OIF? Care of an Osteogenesis Imperfecta Baby and Child.

    Science.gov (United States)

    Ostegenesis Imperfecta Foundation, Inc., Manchester, NH.

    Three pamphlets provide basic information on the care and education of children with osteogenesis imperfecta (OI) a lifelong liability to fractures due to imperfectly formed "brittle bones." The first brochure, a guide to education for children with OI, addresses the importance of attitudes, the value of early education, public school…

  16. A type IV osteogenesis imperfecta family and pregnancy: a case report and literature review

    Institute of Scientific and Technical Information of China (English)

    FENG Zhao-yi; CHEN Qian; SHI Chun-yan; WEN Hong-wu; MA Ke; YANG Hui-xia

    2012-01-01

    Osteogenesis imperfecta is a group of inherited connective-tissue disorders in which synthesis or structure of type Ⅰ collagen is defective and causes osseous fragility.Type Ⅳ osteogenesis imperfecta is dominant inheritance.Here,we report a case of type Ⅳ osteogenesis imperfecta family and their female member's pregnancy.Abnormal sonographic findings (marked bowing and shortening of long bones) and family history made the diagnosis of fetus with osteogenesis imperfecta.The parents decided to give up rescuing the infant and a caesarean section at 27 weeks of gestation was implemented.n conclusion,it is possible to make a prenatal diagnosis of osteogenesis imperfecta by ultrasound.For the pregnant women with osteogenesis imperfecta,management decision should be made on an individual basis.

  17. A type IV osteogenesis imperfecta family and pregnancy: a case report and literature review.

    Science.gov (United States)

    Feng, Zhao-yi; Chen, Qian; Shi, Chun-yan; Wen, Hong-wu; Ma, Ke; Yang, Hui-xia

    2012-04-01

    Osteogenesis imperfecta is a group of inherited connective-tissue disorders in which synthesis or structure of type I collagen is defective and causes osseous fragility. Type IV osteogenesis imperfecta is dominant inheritance. Here, we report a case of type IV osteogenesis imperfecta family and their female member's pregnancy. Abnormal sonographic findings (marked bowing and shortening of long bones) and family history made the diagnosis of fetus with osteogenesis imperfecta. The parents decided to give up rescuing the infant and a caesarean section at 27 weeks of gestation was implemented. In conclusion, it is possible to make a prenatal diagnosis of osteogenesis imperfecta by ultrasound. For the pregnant women with osteogenesis imperfecta, management decision should be made on an individual basis.

  18. [Osteogenesis imperfecta and dentinogenesis imperfecta: diagnostic frontiers and importance in dentofacial orthopedics].

    Science.gov (United States)

    Kamoun-Goldrat, Agnès S; Le Merrer, Martine F

    2007-06-01

    Osteogenesis imperfecta is a genetic disease that varies in severity and is characterized by fragile bones that fracture easily. Many extra-skeletal manifestations can be noted such as blue sclerotic markings, dentinogenesis imperfecta and impaired hearing or deafness. In most cases, an anomaly of collagen is the cause. It is usually accompanied by a specific Class III type cranio-facial morphology with open bite and increased incidence of impacted permanent molars. Orthodontists called upon to treat the dental aspects of this malady, should be careful to protect their patients against bacterial infection and hemorrhages, and to be well aware of the side affects that can be caused by the biophosphanates that constitute the basis of current medical treatment of osteogenesis imperfecta.

  19. Anesthetic Management in a Gravida with Type IV Osteogenesis Imperfecta

    Directory of Open Access Journals (Sweden)

    Elizabeth Vue

    2016-01-01

    Full Text Available Osteogenesis imperfecta (OI is an inherited disorder of the connective tissues caused by abnormalities in collagen formation. OI may present many challenges to the anesthesiologist. A literature review reveals a wide range of implications, from basic positioning to management of the difficult airway. We present the anesthetic management of a 25-year-old gravid woman with OI, fetal demise, and possible uterine rupture, admitted for an exploratory laparotomy.

  20. Children with Osteogenesis Imperfecta and Their Life Situation. Report and Documentation.

    Science.gov (United States)

    Brodin, Jane

    Children with osteogenesis imperfecta form a small and relatively unknown group, with 5 to 10 children diagnosed in Sweden each year and a total of around 200 people under the age of 17 having the condition. A questionnaire was completed by families of 24 Swedish children with osteogenesis imperfecta, and three families were interviewed. The…

  1. Pathophysiology and therapeutic options in osteogenesis imperfecta: an update

    Directory of Open Access Journals (Sweden)

    Brizola E

    2016-03-01

    Full Text Available Evelise Brizola,1 Temis M Félix,2 Jay R Shapiro3 1Bone and Osteogenesis Imperfecta Department, Kennedy Krieger Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA; 2Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; 3Osteoporosis and Metabolic Bone Disorders Center, Bethesda, MD, USAAbstract: Osteogenesis imperfecta (OI is a rare, heritable systemic disorder of bone and connective tissue, which in almost 90% of cases is due to mutations affecting the normal synthesis of type I collagen. In 1979, four OI phenotypes were categorized which were inherited as autosomal dominant characteristics. Individuals with OI present both genetic and phenotypic variabilities. Major characteristics of OI are bone fragility, blue sclerae, dentinogenesis imperfecta, short stature, scoliosis, and joint hyperextensibility. Both autosomal dominant and recessive inheritance are now recognized. Advances in molecular diagnosis have led to a major expansion in our understanding of the genetic basis for different OI phenotypes. To date, sequence variants in 17 genes are described as causative of OI. These genes regulate the synthesis of type I collagen pro-alpha polypeptide chains, proteins involved in type I collagen processing in the endoplasmic reticulum and proteins involved in osteoblast function. These new genetic associations have also led to uncertainty with regard to the current classification of OI phenotypes. Bisphosphonates have been widely used to improve bone mass and decrease fractures in both children and adults with OI. While effective in many but not all children when administered for 2–4 years, bisphosphonates have not proven effective in adults with OI. Studies are limited for treatment of adults with teriparatide and denosumab. Advances have been reported in the surgical management of OI. Although the role of physical therapy in the management

  2. Dental management of severe dentinogenesis imperfecta in a mild form of osteogenesis imperfecta.

    Science.gov (United States)

    Stephen, L X G; Beighton, P

    2002-01-01

    Dentinogenesis Imperfecta (DI), in which the teeth are discolored, translucent and brittle, can occur in isolation as a familial trait and as a component of the skeletal dysplasia Osteogenesis Imperfecta (OI). In a Cape Town family, 20 persons in 3 generations had mild OI, with the additional manifestation of severe DI. The family was assessed at the Dental Genetic Unit of the University of the Western Cape and appropriate dental treatment was provided. In this setting, a detailed treatment plan was devised for a severely affected woman. This plan proved to be efficient and cost effective, and the final outcome was pleasing to the patient. Dentinogenesis Imperfecta is not uncommon and may well be encountered in conventional dental practice. The necessary clinical expertise is within the scope of the skills of the general dentist.

  3. Osteogenesis Imperfecta (Type IV with Dental Findings in Siblings

    Directory of Open Access Journals (Sweden)

    Shishir Ram Shetty

    2011-01-01

    Full Text Available Osteogenesis imperfecta (OI is a hereditary disorder characterized by increased tendency for bone fractures due to high fragility. The clinical and radiological features of OI manifest in different age groups, although the disease is congenital in nature. Besides bone fragility, features like laxity of the ligaments, blue sclera, growth retardation, and scoliosis are also observed. In severe cases, respiratory distress and death have been reported. The most important oral finding in OI is the presence of yellowish-brown-coloured brittle teeth characteristic of dentinogenesis imperfecta. Genetic factors play a very important role in the pathogenesis of OI either as a dominant or recessive factor. When a child has OI, there is a 25% chance of the sibling to have the same disorder. We report two cases of OI in siblings born to parents with a history of consanguineous marriage. The clinical and radiological features of the two cases are described in detail.

  4. [PREPARATIONS OF PAMIDRONOVIC ACID IN COMPLEX TREATMENT ON OSTEOGENESIS IMPERFECTA].

    Science.gov (United States)

    Zyma, A M; Guk, Yu M; Magomedov, O M; Gayko, O G; Kincha-Polishchuk, T A

    2015-07-01

    Modern view of drug therapy in the complex treatment of orthopedic manifestations of osteogenesis imperfecta (OI) was submitted. Developed and tested system of drug correction of structural and functional state of bone tissue (BT) using drugs pamidronovic acid, depending on osteoporosis severity and type of disease. Such therapy is appropriate to apply both independently and in conjunction with surgery to correct deformations of long bones of the lower extremities. Effectiveness and feasibility of the proposed methods of drug therapy was proved, most patients resume features walking and support.

  5. MRI-visible pericochlear lesions in osteogenesis imperfecta type I

    Energy Technology Data Exchange (ETDEWEB)

    Ziyeh, S.; Berger, R.; Reisner, K. [Radiologische Klinik, St. Vincentiuskrankenhaeuser, Karlsruhe (Germany)

    2000-10-01

    Osteogenesis imperfecta (OI) is an inherited generalized disorder of type-I collagen synthesis often associated with hearing loss. We present a case of OI type I in which hearing loss led to examination of the temporal bone with MRI. In the osseous otic capsule MRI demonstrated pericochlear lesions with soft tissue signal intensity and contrast enhancement. Changes similar to otosclerosis have been described in the temporal bone of OI patients when applying CT, but reports on MRI findings do not yet exist. (orig.)

  6. Clinical perspectives on osteogenesis imperfecta versus non-accidental injury.

    Science.gov (United States)

    Pereira, Elaine Maria

    2015-12-01

    Although non-accidental injuries (NAI) are more common in cases of unexplained fractures than rare disorders such as osteogenesis imperfecta (OI), ruling out OI and other medical causes of fracture is always indicated. The majority of OI patients can be diagnosed with the help of family history, physical examination, and radiographic findings. In particular, there are a few radiological findings which are seen more commonly in NAI than in OI which may help guide clinician considerations regarding the probability of either of these diagnoses. At the same time, molecular testing still merits careful consideration in cases with unexplained fractures without obvious additional signs of abuse.

  7. Update on the evaluation and treatment of osteogenesis imperfecta.

    Science.gov (United States)

    Harrington, Jennifer; Sochett, Etienne; Howard, Andrew

    2014-12-01

    Osteogenesis imperfecta (OI) is a heritable bone fragility disorder that presents with a wide clinical phenotype spectrum: from perinatal lethality and severe deformities to very mild forms without fractures. Most cases of OI are due to autosomal dominant mutations of the type I collagen genes. A multidisciplinary approach with rehabilitation, orthopedic surgery, and consideration of medical therapy with bisphosphonates underpins current management. Greater understanding of the pathogenesis of OI may lead to novel, therapeutic approaches to help improve clinical symptoms of children with OI in the future.

  8. Perinatal lethal type II osteogenesis imperfecta: a case report.

    Science.gov (United States)

    Ayadi, Imene Dahmane; Hamida, Emira Ben; Rebeh, Rania Ben; Chaouachi, Sihem; Marrakchi, Zahra

    2015-01-01

    We report a new case of osteogenesis imperfecta (OI) type II which is a perinatal lethal form. First trimester ultrasound didn't identified abnormalities. Second trimester ultrasound showed incurved limbs, narrow chest, with hypomineralization and multiple fractures of ribs and long bones. Parents refused pregnancy termination; they felt that the diagnosis was late. At birth, the newborn presented immediate respiratory distress. Postnatal examination and bone radiography confirmed the diagnosis of OI type IIA. Death occurred on day 25 of life related to respiratory failure.

  9. Hyperplastic callus formation in osteogenesis imperfecta: CT and MRI findings

    Energy Technology Data Exchange (ETDEWEB)

    Rieker, O.; Kreitner, K.F. [Klinik fuer Radiologie, Johannes-Gutenberg-Univ. Mainz (Germany); Karbowski, A. [Orthopaedische Abtl., Krankenhaus der Augustinerinnen, Koeln (Germany)

    1998-09-01

    Hyperplastic callus formation is a noteworthy condition in patients with osteogenesis imperfecta because it often mimicks osteosarcoma on radiography. The findings of CT and MRI in hyperplastic callus formation have not been reported. In the presented case, MRI demonstrated contrast enhancement and edema of the surrounding soft tisssue, consistent with benign as well as malignant disease. Computed tomography showed a calcified rim of the lesion which may be a useful feature to rule out osteosarcoma in this condition. (orig.) With 2 figs., 18 refs.

  10. Osteogenesis imperfecta and clubfoot—a rare combination

    OpenAIRE

    Persiani, Pietro; Ranaldi, Filippo Maria; Martini, Lorena; Zambrano, Anna; Celli, Mauro; D’Eufemia, Patrizia; Villani, Ciro

    2016-01-01

    Abstract Background: Osteogenesis imperfecta (OI) is a rare congenital genetic osteodystrophy, which has a prevalence of 1:20,000. OI is caused by the mutation of the COL1A1/COL1A2 genes, leading to a deficit of quality and/or quantity in the synthesis of procollagen-α type 1. Seven different forms of diverse clinical entity have been classified by Sillence and Glorieux, although, recently, up to 11 forms characterized by different genetic mutations have been recognized. Patients with OI suff...

  11. Recent developments in osteogenesis imperfecta [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Joseph L. Shaker

    2015-09-01

    Full Text Available Osteogenesis imperfecta (OI is an uncommon genetic bone disease associated with brittle bones and fractures in children and adults. Although OI is most commonly associated with mutations of the genes for type I collagen, many other genes (some associated with type I collagen processing have now been identified. The genetics of OI and advances in our understanding of the biomechanical properties of OI bone are reviewed in this article. Treatment includes physiotherapy, fall prevention, and sometimes orthopedic procedures. In this brief review, we will also discuss current understanding of pharmacologic therapies for treatment of OI.

  12. Osteogenesis imperfecta due to compound heterozygosity for the LEPRE1 gene.

    Science.gov (United States)

    Moul, Adrienne; Alladin, Amanda; Navarrete, Cristina; Abdenour, George; Rodriguez, Maria M

    2013-10-01

    Osteogenesis imperfecta is a rare connective tissue disorder characterized by bone fragility and low bone density. Most cases are caused by an autosomal dominant mutation in either COL1A1 or COL1A2 gene encoding type I collagen. However, autosomal recessive forms have been identified. We present a patient with severe respiratory distress due to osteogenesis imperfecta simulating type II, born to a non-consanguineous couple with mixed African-American and African-Hispanic ethnicity. Cultured skin fibroblasts demonstrated compound heterozygosity for mutations in the LEPRE1 gene encoding prolyl 3-hydroxylase 1 confirming the diagnosis of autosomal recessive osteogenesis imperfecta type VIII, perinatal lethal type.

  13. An unusual presentation of osteogenesis imperfecta type I

    Directory of Open Access Journals (Sweden)

    Rebelo M

    2011-04-01

    Full Text Available Marta Rebelo, Jandira Lima, José Diniz Vieira, José Nascimento CostaDepartment of Internal Medicine, University Hospital of Coimbra, Coimbra, PortugalAbstract: Osteogenesis imperfecta (OI is a rare inherited disorder with a broad spectrum of clinical and genetic variability. The genetic diversity involves, in the majority of the cases, mutations in one of the genes that encodes the type 1 collagen protein (COL1 A1 and COL1 A2, but it is not a requirement for the diagnosis. The most benign form is OI type I. The authors present a case report of a 25-year-old woman who had severe low back pain associated with incapacity to walk and breast-feed post-partum. Symptoms developed 2 weeks after delivery. The radiological examination revealed severe osteoporosis with no abnormalities in the laboratory findings. The clinical signs and a positive personal and family history of multiple fractures in childhood suggested OI type I, although other diagnosis, such as pregnancy-associated osteoporosis, was also considered. The atypical presentation of this rare disorder in adulthood calls attention to the need for early diagnosis for prompt treatment. Treatment of OI is never curative, but it improves the quality of the patient’s life.Keywords: osteogenesis imperfecta, collagen, pregnancy, osteoporosis

  14. Orthopaedic Considerations for the Adult With Osteogenesis Imperfecta.

    Science.gov (United States)

    Roberts, Timothy T; Cepela, Daniel J; Uhl, Richard L; Lozman, Jeffery

    2016-05-01

    Osteogenesis imperfecta is a heritable group of collagen-related disorders that affects up to 50,000 people in the United States. Although the disease is most symptomatic in childhood, adults with osteogenesis imperfecta also are affected by the sequelae of the disease. Orthopaedic manifestations include posttraumatic and accelerated degenerative joint disease, kyphoscoliosis, and spondylolisthesis. Other manifestations of abnormal collagen include brittle dentition, hearing loss, cardiac valve abnormalities, and basilar invagination. In general, nonsurgical treatment is preferred for management of acute fractures. High rates of malunion, nonunion, and subsequent deformity have been reported with both closed and open treatment. When surgery is necessary, surgeons should opt for load-sharing intramedullary devices that span the entire length of the bone; locking plates and excessively rigid fixation generally should be avoided. Arthroplasty may be considered for active patients, but the procedure frequently is associated with complications in this patient population. Underlying deformities, such as malunion, bowing, rotational malalignment, coxa vara, and acetabular protrusio, pose specific surgical challenges and underscore the importance of preoperative planning.

  15. Osteogenesis imperfecta%成骨不全

    Institute of Scientific and Technical Information of China (English)

    Michael P Whyte; 邢小平

    2004-01-01

    骨组织的结构极为复杂,包含矿物质和不同的有机物质,其中包括胶原。I型胶原是骨骼中的主要蛋白质,在软骨中存在Ⅱ、Ⅸ、X和Ⅺ型胶原。成骨不全(osteogenesis imperfecta,OI,脆骨病)是最常见的骨基质异常,是一种遗传性疾病。几乎所有的病例都存在I型胶原质和量的异常。其严重程度不

  16. Current and emerging treatments for the management of osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Elena Monti

    2010-08-01

    Full Text Available Elena Monti1, Monica Mottes1, Paolo Fraschini2, PierCarlo Brunelli3, Antonella Forlino4, Giacomo Venturi1, Francesco Doro1, Silvia Perlini1, Paolo Cavarzere1, Franco Antoniazzi11Department of Life Sciences and Reproduction, Pediatric Clinic University of Verona, Verona, Italy; 2Istituto Di Ricovero e Cura a Carattere Scientifico, ‘E. Medea’, Associazione La Nostra Famiglia, Bosisio Parini (LC, Italy; 3Divisione di Ortopedia Pediatrica, Spedali Civili, Brescia, Italy; 4Department of Biochemistry “A. Castellani”, University of Pavia, ItalyAbstract: Osteogenesis imperfecta (OI is the most common bone genetic disorder and it is characterized by bone brittleness and various degrees of growth disorder. Clinical severity varies widely; nowadays eight types are distinguished and two new forms have been recently described although not yet classified. The approach to such a variable and heterogeneous disease should be global and therefore multidisciplinary. For simplicity, the objectives of treatment can be reduced to three typical situations: the lethal perinatal form (type II, in which the problem is survival at birth; the severe and moderate forms (types III–IX, in which the objective is ‘autonomy’; and the mild form (type I, in which the aim is to reach ‘normal life’. Three types of treatment are available: non-surgical management (physical therapy, rehabilitation, bracing and splinting, surgical management (intramedullary rod positioning, spinal and basilar impression surgery and medical-pharmacological management (drugs to increase the strength of bone and decrease the number of fractures as bisphosphonates or growth hormone, depending on the type of OI. Suggestions and guidelines for a therapeutic approach are indicated and updated with the most recent findings in OI diagnosis and treatment.Keywords: osteogenesis imperfecta, bone genetic disorder, bone brittleness, “brittle bone disease”, connective tissue malfunction, short

  17. Pediatric dental management of a patient with osteogenesis imperfecta and dentinogenesis imperfecta.

    Science.gov (United States)

    Muhney, Kelly; Campbell, Patricia Regener

    2007-01-01

    Osteogenesis imperfecta (OI) is a genetic disorder that affects all connective tissue. Clinical manifestations of OI include bone fragility, hyperlaxity of joints, hearing loss, abnormalities of stature and facial structure, blue sclerae, and dentinogenesis imperfecta (DI). OI is classified into four groups according to the severity and physical characteristics of the disease, although not all characteristics may be present in one individual. Currently, 20,000 to 50,000 individuals in the U.S. have been diagnosed with this disease. The aim of this article is to discuss medical and dental complications associated with OI and DI. A case presentation describes the clinical care of a patient from birth to age 12.

  18. Osteogenesis imperfecta types I-XI: implications for the neonatal nurse.

    Science.gov (United States)

    Womack, Jody

    2014-10-01

    Osteogenesis imperfecta (OI), also called "brittle bone disease," is a rare heterozygous connective tissue disorder that is caused by mutations of genes that affect collagen. Osteogenesis imperfecta is characterized by decreased bone mass, bone fragility, and skin hyperlaxity. The phenotype present is determined according to the mutation on the affected gene as well as the type and location of the mutation. Osteogenesis imperfecta is neither preventable nor treatable. Osteogenesis imperfecta is classified into 11 types to date, on the basis of their clinical symptoms and genetic components. This article discusses the definition of the disease, the classifications on the basis of its clinical features, incidence, etiology, and pathogenesis. In addition, phenotype, natural history, diagnosis and management of this disease, recurrence risk, and, most importantly, the implications for the neonatal nurse and management for the family are discussed.

  19. Basilar impression and osteogenesis imperfecta in a three-year-old girl: CT and MRI

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    Rush, P.J.; Berbrayer, D.; Reilly, B.J.

    1989-01-01

    A 3-year-old girl with osteogenesis imperfecta developed symptomatic basilar impression. Her neurological symptoms were treated by foramen magnum decompression and laminectomy. This is an unusually young patient to have this condition.

  20. Stapedotomy in osteogenesis imperfecta : a prospective study of 32 consecutive cases

    NARCIS (Netherlands)

    Vincent, Robert; Wegner, Inge; Stegeman, Inge; Grolman, Wilko

    2014-01-01

    OBJECTIVE: To prospectively evaluate hearing outcomes in patients with osteogenesis imperfecta undergoing primary stapes surgery and to isolate prognostic factors for success. STUDY DESIGN: A nonrandomized, open, prospective case series. SETTING: A tertiary referral center. PATIENTS: Twenty-five con

  1. End-stage posttraumatic osteoarthritis treated with THA in osteogenesis imperfecta.

    Science.gov (United States)

    Chaus, George W; Heare, Travis

    2012-06-01

    Osteogenesis imperfecta is an incurable genetic disorder manifested with altered bone quality that predisposes patients to a multitude of fractures throughout their lives, including acetabular fractures. The management of acetabular fractures in patients with osteogenesis imperfecta remains a challenging clinical problem, with a paucity of literature supporting treatments and their outcomes. Limited reports in the literature validate the use of total hip arthroplasty (THA) in patients with osteogenesis imperfecta, and they describe the adult population only.This article describes a case of delayed diagnosis of a transverse acetabular fracture and femoral head impaction fracture that led to posttraumatic end-stage hip osteoarthritis in a 16-year-old boy with osteogenesis imperfecta (Sillence Type I) that was sustained after minimal trauma. Clinical examination 3 months postinjury revealed a significant pelvic obliquity, severe pain with hip range of motion, and limited hip range of motion. Imaging studies revealed a complete loss of articular cartilage and significant joint effusion.The patient underwent THA. No postoperative complications occurred. Two-year follow-up showed an excellent clinical result. The patient's hip was pain free, and he was able to walk with no limp.The authors are unaware of any reported cases of children with osteogenesis imperfecta undergoing THA. Based on the reported literature and the authors' experience, THA can be a reliable surgical option for patients with osteogenesis imperfecta.

  2. Heart disease in patients with osteogenesis imperfecta - A systematic review

    DEFF Research Database (Denmark)

    Ashournia, Hamoun; Johansen, Frank Ted; Folkestad, Lars

    2015-01-01

    INTRODUCTION: Osteogenesis imperfecta (OI) is a rare, inherited systemic connective tissue disease that causes decreased bioavailability of collagen type 1. Collagen type 1 is the most abundant connective tissue in the body and a key part of many organs. While the bone phenotype in OI is well...... described, less is known about the effects of decreased collagen on other organs. In the heart, collagen type 1 is present in the heart valves, chordae tendineae, annuli fibrosi and the interventricular septum. It is thus likely that the heart is affected in OI. OBJECTIVES: The aim of this systematic...... of 68 studies were included in the review, comprising 51 case reports, 8 small case series (ncase series (n≥10 patients) and 5 cross-sectional studies comparing patients and controls. Together, the papers comprised 499 patients and covered 45years of medical literature. The most...

  3. Prenatal transplantation of mesenchymal stem cells to treat osteogenesis imperfecta.

    Directory of Open Access Journals (Sweden)

    Jerry KY Chan

    2014-10-01

    Full Text Available Osteogenesis Imperfecta (OI can be a severe disorder that can be diagnosed before birth. Transplantation of mesenchymal stem cells (MSC has the potential to improve the bone structure, growth and fracture healing. In this review we give an introduction to OI and MSC, and the basis for prenatal and postnatal transplantation in OI. We also summarize the two patients with OI who has received prenatal and postnatal transplantation of MSC.The findings suggest that prenatal transplantation of allogeneic MSC in OI is safe. The cell therapy is of likely clinical benefit with improved linear growth, mobility and reduced fracture incidence. Unfortunately, the effect is transient. For this reason postnatal booster infusions using same-donor MSC have been performed with clinical benefit, and without any adverse events.So far there is limited experience in this specific field and proper studies are required to accurately conclude on clinical benefits of MSC transplantation to treat OI.

  4. Advances in the Classification and Treatment of Osteogenesis Imperfecta.

    Science.gov (United States)

    Thomas, Inas H; DiMeglio, Linda A

    2016-02-01

    Osteogenesis imperfecta (OI) is a rare disorder of type 1 collagen with 13 currently identified types attributable to inherited abnormalities in type 1 collagen amount, structure, or processing. The disease is characterized by an increased susceptibility to bony fracture. In addition to the skeletal phenotype, common additional extraskeletal manifestations include blue sclerae, dentinogenesis imperfecta, vascular fragility, and hearing loss. Medical management is focused on minimizing the morbidity of fractures, pain, and bone deformities by maximizing bone health. Along with optimizing Vitamin D status and calcium intake and physical/occupational therapy, individualized surgical treatment may be indicated. Pharmacological therapy with bisphosphonate medications is now routinely utilized for moderate to severe forms and appears to have a good safety profile and bone health benefits. New therapies with other anti-resorptives as well as anabolic agents and transforming growth factor (TGF)β antibodies are in development. Other potential treatment modalities could include gene therapy or mesenchymal cell transplant. In the future, treatment choices will be further individualized in order to reduce disease morbidity and mortality.

  5. Hearing Loss in Osteogenesis Imperfecta: Characteristics and Treatment Considerations

    Directory of Open Access Journals (Sweden)

    Joseph P. Pillion

    2011-01-01

    Full Text Available Osteogenesis imperfecta (OI is the most common heritable disorder of connective tissue. It is associated with fractures following relatively minor injury, blue sclerae, dentinogenesis imperfecta, increased joint mobility, short stature, and hearing loss. Structures in the otic capsule and inner ear share in the histologic features common to other skeletal tissues. OI is due to mutations involving several genes, the most commonly involved are the COL1A1 or COL1A2 genes which are responsible for the synthesis of the proalpha-1 and proalpha-2 polypeptide chains that form the type I collagen triple helix. A genotype/phenotype relationship to hearing loss has not been established in OI. Hearing loss is commonly found in OI with prevalence rates ranging from 50 to 92% in some studies. Hearing loss in OI may be conductive, mixed, or sensorineural and is more common by the second or third decade. Treatment options such as hearing aids, stapes surgery, and cochlear implants are discussed.

  6. Clinical and Molecular Characterization of Osteogenesis Imperfecta Type V

    Science.gov (United States)

    Brizola, Evelise; Mattos, Eduardo P.; Ferrari, Jessica; Freire, Patricia O.A.; Germer, Raquel; Llerena Jr, Juan C.; Félix, Têmis M.

    2015-01-01

    Osteogenesis imperfecta type V (OI-V) has a wide clinical variability, with distinct clinical/radiological features, such as calcification of the interosseous membrane (CIM) between the radius-ulna and/or tibia-fibula, hyperplastic callus (HPC) formation, dislocation of the radial head (DRH), and absence of dentinogenesis imperfecta (DI). Recently, a single heterozygous mutation (c.-14C>T) in the 5′UTR of the IFITM5 gene was identified to be causative for OI-V. Here, we describe 7 individuals from 5 unrelated families that carry the c.-14C>T IFITM5 mutation. The clinical findings in these cases are: absence of DI in all patients, presence of blue sclera in 2 cases, and 4 patients with DRH. Radiographic findings revealed HPC in 3 cases. All patients presented CIM between the radius and ulna, while 4 patients presented additional CIM between the tibia and fibula. Spinal fractures by vertebral compression were observed in all individuals. The proportion of cases identified with this mutation represents 4% of OI cases at our institution. The clinical identification of OI-V is crucial, as this mutation has an autosomal dominant inheritance with variable expressivity. PMID:26648832

  7. Osteogenesis Imperfecta in Adult Twins Responded To Treatment With Pamidronate

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    Mehtap Çakır

    2011-06-01

    Full Text Available Bisphosphonates are strong inhibitors of bone resorption and are used in the treatment of osteoporosis. Bisphosphonates are known to be effective in prevention of fractures, improvement of bone mineral density as well as in relieving bone pain in osteogenesis imperfecta (OI patients. Recent studies have shown that especially intravenous pamidronate may be more effective when given in childhood and adolescence. This effect was also shown in adult OI patients in some clinical trials.22-year-old twin brothers known to have OI were admitted to our endocrinology and metabolism outpatient clinic. On medical history, OI was diagnosed at the age of three and for the last eight years, they were not able to walk and were using wheelchairs. On physical examination, blue sclerae and dentinogenesis imperfecta were detected in both patients. According to the expanded Sillence classification of OI, the clinical findings were consistent with type IV OI. Intravenous pamidronate treatment was given three times at four-month intervals, according to Montreal protocol. During this period, the patients were also doing isometric exercises and were on physical therapy, diet, and bioresonance therapy.At the end of one year, bone pain regressed significantly in both patients and they were able to walk independently. These outcomes demonstrate that in selected adult OI patients, intravenous pamidronate treatment may be beneficial in preventing bone fractures and relieving pain. Türk Jem 2011; 15: 39-43

  8. Mutations in FKBP10 can cause a severe form of isolated Osteogenesis imperfecta

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    Steinlein Ortrud K

    2011-11-01

    Full Text Available Abstract Background Mutations in the FKBP10 gene were first described in patients with Osteogenesis imperfecta type III. Two follow up reports found FKBP10 mutations to be associated with Bruck syndrome type 1, a rare disorder characterized by congenital contractures and bone fragility. This raised the question if the patients in the first report indeed had isolated Osteogenesis imperfecta or if Bruck syndrome would have been the better diagnosis. Methods The patients described here are affected by severe autosomal recessive Osteogenesis imperfecta without contractures. Results Homozygosity mapping identified FKBP10 as a candidate gene, and sequencing revealed a base pair exchange that causes a C-terminal premature stop codon in this gene. Conclusions Our study demonstrates that FKBP10 mutations not only cause Bruck syndrome or Osteogenesis imperfecta type III but can result in a severe type of isolated Osteogenesis imperfecta type IV with prenatal onset. Furthermore, it adds dentinogenesis imperfecta to the spectrum of clinical symptoms associated with FKBP10 mutations.

  9. Radiation therapy of hyperplastic heterotopic ossifications in osteogenesis imperfecta; Two case reports. Strahlentherapie hyperplastischer heterotoper Ossifikationen bei Osteogenesis imperfecta; Zwei Falldarstellungen

    Energy Technology Data Exchange (ETDEWEB)

    Micke, O. (Muenster Univ. (Germany). Klinik und Poliklinik fuer Strahlentherapie - Radioonkologie); Wagner, W. (Muenster Univ. (Germany). Klinik und Poliklinik fuer Strahlentherapie - Radioonkologie); Poetter, R. (Allgemeines Krankenhaus der Stadt Wien, Vienna (Austria). Universitaetsklinik fuer Strahlentherapie und Strahlenbiologie); Prott, F.J. (Muenster Univ. (Germany). Klinik und Poliklinik fuer Strahlentherapie - Radioonkologie); Karbowski, A. (Muenster Univ. (Germany). Klinik und Poliklinik fuer Allgemeine Orthopaedie)

    1994-06-01

    Purpose: Osteogenesis imperfecta is a rare hereditary disease of connective tissue with a genetic defect in collagen synthesis. In osteogenesis imperfecta hyperplastic heterotopic ossification can be induced by hyperplastic callus formation caused by trauma or operation. Heterotopic ossifications can be found in numerous benign diseases. The successful use of low dose radiotherapy in the treatment of heterotopic ossifications in well-known from the literature. Patients and Methods: We treated two children (a 13-year old girl and a ten-year old boy) with heterotopic ossifications of the lower extremities in osteogenesis imperfecta type IV (Lobstein) with a low dose irradiation (10x1 Gy, respectively 6x1 Gy) under megavoltage conditions. Results: After radiotherapy the children were painfree and the hyperplastic callus was considerably reduced. The previously immobilized patients could partly be mobilized. Thereby it could be contributed to the rehabilitation of the patients. New hyperplastic callus formation was not observed in the irradiated areas so far. Conclusion: Analogous to the successful radiation of heterotopic ossifications in other benign diseases radiation therapy seems to be a successful treatment of hyperplastic callus formation in osteogenesis imperfecta. Despite the late risks of radiotherapy radiation treatment of benign diseases in children might be indicated. (orig.)

  10. COL1A2 gene analysis in a Czech osteogenesis imperfecta patient: a candidate novel mutation in a patient affected by osteogenesis imperfecta type 3

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    Hrušková L

    2015-08-01

    Full Text Available Lucie Hrušková,1 Ivo Mařík,2,3 Stella Mazurová,1 Pavel Martásek,1 Ivan Mazura1 1Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic; 2Ambulant Centre for Defects of Locomotor Apparatus 1.1.c., Prague, Czech Republic; 3Faculty of Medical Studies, West Bohemia University, Pilsen, Czech RepublicAbstract: Osteogenesis imperfecta is a heritable bone fragility disease with a heterogenic genetic origin. Most cases result from mutations of either the COL1A1 gene or the COL1A2 gene. We identified a novel COL1A2 gene mutation in a Czech patient, born to unaffected parents, who was diagnosed according to clinical and anthropometric findings and radiographic features as having type 3 osteogenesis imperfecta, which is a severe form of this disease. The identified Gly814Trp mutation was predicted by a number of complementary bioinformatic programs to result in functional alteration of the protein. This case report provides both evidence of a novel COL1A2 mutation resulting in type 3 osteogenesis imperfecta and a genotype:phenotype correlation in this affected individual. Keywords: osteogenesis imperfecta type 3, collagen, alpha-2 (I chain, substitution, sequencing 

  11. Asymptomatic parental mosaicism for osteogenesis imperfecta associated with a new splice site mutation in COL1A2

    OpenAIRE

    2016-01-01

    Key Clinical Message Recurrent lethal perinatal osteogenesis imperfecta may result from asymptomatic parental mosaicism. A previously unreported mutation in COL1A2 leads to recurrent cases of fetal osteogenesis imperfecta Sillence type IIA, which emphasizes the importance of clinical and genetic evaluation of mosaicism in asymptomatic parents as verified mosaicism highly increases recurrence risk.

  12. [Postoperative radiation therapy for a patient with osteogenesis imperfecta: case report].

    Science.gov (United States)

    Ducournau, A; Lagarde, P; Henriques de Figueiredo, B; Antoine, M; Breton-Callu, C; Petit, A; Dallaudière, B; Sargos, P

    2014-03-01

    Osteogenesis imperfecta is an unusual disease also called Lobstein disease. Characterized by abnormalities of collagen biosynthesis, a possible mutation on 17th chromosome is described. On the other hand, 29% of breast cancers present a mutation on the same chromosome. Nevertheless, the association of osteogenesis imperfecta and breast cancer is at the moment unknown. Therapeutic management is very difficult because of a loss in dihydropyrimidine dehydrogenase for patients having osteogenesis imperfecta, generating some toxicity by default in catabolism of 5-fluorouracil. We report the case of a 49-year-old woman with a breast cancer in the context of osteogenesis imperfecta. Dosimetric considerations permitting to reduce chess dose level have been performed for this patient. With a follow-up of 6 months, no imaging fracture has been revealed after radiotherapy. No evident conclusion about radiation injury from a case report could be described in case of osteogenesis imperfecta. To our knowledge, this is the first case which take into account potential radiation induced toxicities.

  13. Clinical manifestations and dental management of dentinogenesis imperfecta associated with osteogenesis imperfecta: Case report.

    Science.gov (United States)

    Abukabbos, Halima; Al-Sineedi, Faisal

    2013-10-01

    Dentinogenesis imperfecta (DI) associated with osteogenesis imperfecta (OI) is a genetic disorder that affects the connective tissues and results in dentine dysplasia. This case report discusses the systemic and dental manifestations of OI and DI in a 4-year-old child, with moderate presentation of both disorders, who was treated at King Fahd Military Medical Complex in Dhahran. Dental treatment included the use of strip and stainless-steel crowns under local anesthesia, as well as behavior modification techniques. Rigorous home care instructions, including reinforcement of the oral hygiene practice and avoidance of any episode that may lead to bone fracture, were discussed with the parents. The case was reevaluated at 3-month follow-up visits, wherein the medical and dental histories were updated, the child's growth was monitored, periodic clinical and radiographic examinations were performed, and the oral hygiene was evaluated via the debris index score and caries risk assessment. Further treatment of the permanent dentition may be needed in the future.

  14. Whole exome sequencing reveals a mutation in an osteogenesis imperfecta patient

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    Mehmet Ali Ergun

    2017-02-01

    Full Text Available Osteogenesis imperfecta (OI is an autosomal dominant disorder characterized mainly by bone fragility and blue sclerae. OI is caused by mutations in type I collagen genes, COL1A1 and COL1A2. Dentinogenesis imperfecta is a common disorder for osteogenesis imperfecta patients. More than half of the OI patients have also dentinogenesis imperfecta. Whole exome sequencing (WES, involves exome capture, which limits sequencing of the protein coding regions of the genome, composed of about 20,000 genes, 180,000 exons, and constituting approximately 1% of the whole genome. A major indication for use is molecular diagnosis of patients with suspected genetic disorders or of patients with known genetic disorders with substantial genetic heterogeneity involving substantial gene complexity. In this study, we performed WES for a patient prediagnosed as Osteogenesis imperfecta. He had also dentinogenesis imperfecta. The WES results confirmed with Sanger sequencing revealed as a missense mutation at codon 560 of COL1A1 gene: c.1678G>A p.(Gly560Cys. The mutation was in exon 25 and according to the dbSNP database this mutation corresponded to rs67507747. As a conclusion, it is very important to perform WES after an algorithm. This algorithm has to include, a suspect of a mendelian disorder, multiple genetic conditions in the differential diagnosis, and even if it is available the conventional diagnosis is prohibitively expensive. Finally, Sanger sequencing in order to confirm the results is also advised.

  15. Osteogenesis Imperfecta Type VI in Individuals from Northern Canada.

    Science.gov (United States)

    Ward, Leanne; Bardai, Ghalib; Moffatt, Pierre; Al-Jallad, Hadil; Trejo, Pamela; Glorieux, Francis H; Rauch, Frank

    2016-06-01

    Osteogenesis imperfecta (OI) type VI is a recessively inherited form of OI that is caused by mutations in SERPINF1, the gene coding for pigment-epithelium derived factor (PEDF). Here, we report on two apparently unrelated children with OI type VI who had the same unusual homozygous variant in intron 6 of SERPINF1 (c.787-10C>G). This variant created a novel splice site that led to the in-frame addition of three amino acids to PEDF (p.Lys262_Ile263insLeuSerGln). Western blotting showed that skin fibroblasts with this mutation produced PEDF but failed to secrete it. Both children were treated with intravenous bisphosphonates, but the treatment of Individual 1 was switched to subcutaneous injections of denosumab (dose 1 mg per kg body weight, repeated every 3 months). An iliac bone sample obtained after 5 denosumab injections (and 3 months after the last injection) showed no change in the increased osteoid parameters that are typical of OI type VI, but the number of osteoclasts in trabecular bone was markedly increased. This suggests that the effect of denosumab on osteoclast suppression is of shorter duration in children with OI type VI than what has previously been reported on adults with osteoporosis.

  16. Osteogenesis imperfecta: clinical diagnosis, nomenclature and severity assessment.

    Science.gov (United States)

    Van Dijk, F S; Sillence, D O

    2014-06-01

    Recently, the genetic heterogeneity in osteogenesis imperfecta (OI), proposed in 1979 by Sillence et al., has been confirmed with molecular genetic studies. At present, 17 genetic causes of OI and closely related disorders have been identified and it is expected that more will follow. Unlike most reviews that have been published in the last decade on the genetic causes and biochemical processes leading to OI, this review focuses on the clinical classification of OI and elaborates on the newly proposed OI classification from 2010, which returned to a descriptive and numerical grouping of five OI syndromic groups. The new OI nomenclature and the pre-and postnatal severity assessment introduced in this review, emphasize the importance of phenotyping in order to diagnose, classify, and assess severity of OI. This will provide patients and their families with insight into the probable course of the disorder and it will allow physicians to evaluate the effect of therapy. A careful clinical description in combination with knowledge of the specific molecular genetic cause is the starting point for development and assessment of therapy in patients with heritable disorders including OI. © 2014 The Authors. American Journal of Medical Genetics Published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

  17. Mortality and Causes of Death in Patients With Osteogenesis Imperfecta

    DEFF Research Database (Denmark)

    Folkestad, Lars; Hald, Jannie Dahl; Canudas-Romo, Vladimir;

    2016-01-01

    Osteogenesis imperfecta (OI) is a hereditary connective tissue disease that causes frequent fractures. Little is known about causes of death and length of survival in OI. The objective of this work was to calculate the risk and cause of death, and the median survival time in patients with OI...... five to one to the OI cohort. We calculated hazard ratios for all-cause mortality and subhazard ratios for cause-specific mortality in a comparison of the OI cohort and the reference population. We also calculated all-cause mortality hazard ratios for males, females, and age groups (0 to 17.99 years......, 18.00 to 34.99 years, 35.00 to 54.99 years, 55.00 to 74.99 years, and >75 years). We identified 687 cases of OI (379 women) and included 3435 reference persons (1895 women). A total of 112 patients with OI and 257 persons in the reference population died during the observation period. The all-cause...

  18. Roentgenographic Evaluation of the Spine in Patients With Osteogenesis Imperfecta

    Science.gov (United States)

    de Lima, Marcos Vaz; de Lima, Fabiana Vaz; Akkari, Miguel; de Resende, Vanessa Ribeiro; Santili, Claudio

    2015-01-01

    Abstract Osteogenesis imperfecta (OI) is a hereditary connective tissue disorder that leads to bone weakness and deformities, especially in the spine, which can lead to poor outcomes. The aim of this study was to find patterns and risk factors in spinal deformities in patients with OI. In a retrospective study, 70 patients with OI were selected. Radiographs of the spine were evaluated. We observed the presence or absence of the following changes: biconcave vertebrae, chest and vertebral deformities, unilateral rib, and thoracolumbar kyphosis. The greater curve was considered the primary one, and the secondary curve considered compensatory. In the study sample, we observed that the patients’ ages ranged between 7 and 50 years, with a mean equal to 13 years, and 76% had scoliosis. In 68% of cases the main curve in the thoracic region was observed with the convexity to the right. The following was found in patients with OI: scoliosis, biconcave vertebrae, vertebral and chest deformity, unilateral rib, and thoracolumbar kyphosis. The thoracolumbar kyphosis is highly associated with thoracic hypokyphosis in patients with OI. PMID:26632680

  19. Successful operative rib fixation of traumatic flail chest in a patient with osteogenesis imperfecta.

    Science.gov (United States)

    Kulaylat, Afif N; Chesnut, Charles H; Santos, Ariel P; Armen, Scott B

    2014-09-01

    Increasing attention has been directed towards operative rib fixation of traumatic flail chest; reported benefits include more rapid weaning from the ventilator, decreased intensive care unit stays, decreased complications and improved functional results. The outcomes of this surgical intervention in patients with osteogenesis imperfecta, a rare condition characterized by low bone density and bone fragility, are unknown. This case demonstrates that, in the management of traumatic flail chest in a patient with osteogenesis imperfecta, surgical fixation can be successful and should be considered early.

  20. Tratamiento de osteogénesis imperfecta con bisfosfonatos Treatment of osteogenesis imperfecta with bisphosphonates

    Directory of Open Access Journals (Sweden)

    Cristina Tau

    2007-08-01

    Full Text Available El tratamiento con bisfosfonatos (BP, ha mejorado la calidad de vida de los pacientes con osteogénesis imperfecta (OI. Los efectos benéficos son el alivio del dolor, la reducción de la incidencia de fracturas, la mejor movilidad corporal y la recuperación en las formas vertebrales. El tratamiento es más efectivo durante el período de crecimiento. Se presenta una actualización del tema. De la lectura de los anales se destacan los siguientes interrogantes: ¿Por cuánto tiempo deberá instituirse el tratamiento? ¿Es la vía oral tan efectiva como la endovenosa? ¿Cuál es la mejor dosis? ¿Cuándo suspender el tratamiento? ¿Se conservará la integridad del tejido óseo después de un tratamiento prolongado? ¿Qué fenómenos ocurren en el tejido óseo después de la interrupción de la terapia?.Treatment with bisphosphonates (BP improves the quality of life of patients with osteogenesis imperfecta (OI. Beneficial effects are the relief of bone pain, a reduction of fracture incidence, improvement of corporal mobility and recovery of normal vertebral form. Treatment is less effective after completion of growth is here. An update of the literature is here presented. A number of important unsolved questions have been pointed out: for how long should treatment be instituted? Is the oral route as effective as the intravenous one? Which is the best dose? When treatment should be stopped? How well preserved is the longterm integrity of the bones? Which are the phenomena occurring in bone tissue after interruption of therapy?.

  1. AB129. Osteogenesis imperfecta: clinical features and bisphosphonate treatment outcome

    Science.gov (United States)

    Can, Ngoc Thi Bich; Vu, Dung Chi; Bui, Thao Phuong; Nguyen, Khanh Ngoc

    2015-01-01

    Background and objective Osteogenesis imperfecta (OI) comprises a group of disorders principally affecting type I collagen which result in increased bone fragility. Children with severe OI suffer recurrent fractures, resulting in severe deformity and growth stunting in many cases, with loss of independent ambulation by the teenage years in over 50% of cases. Recently, cyclical intravenous treatment with pamidronate has proven of benefit to children with severe forms of OI. This article aims to describle clinical features and laboratory manifestations of patient with OI and evaluate outcome of bisphosphonate management. Methods Clinical features, biochemical finding, and management outcome of 104 cases were study. The patients were classified into four major subtypes of Sillience et al. 1979. Patients with severe types were treatment with pamidronate (Aredia) used Rauch protocol 2003. Results Now we have 196 patients (87 females and 109 males) but we studied focus on 104 patients from 98 families (60 males, 44 females) onset at 2.1±3.0 years (median 0.35) with the average fracture bone of 5.9±4.4 times. In there, 17% type I, 8% type II, 63% type III, and 12% type IV. Clinical features include of intrauterine fracture visible on ultrasound 35%, bone deformation after birth 68%, triangle face 76%, long bone deformation 91%, chest deformation 46%, scoliosis 27%, short status 90%, blue sclera 83%, dentinogenesis imperfecta 20%, hearing loss 6%. Thirty patients have been treated with pamidronate at 3.2±3.7 years (4 months to 8 years) during 13±0.8 months (6-30 months). Fourteen patients had fracture bone after 6 months of treatment but no patients had fracture bone after 12 months. Seven patients had been treatment after 1.6±0.5 years, BMD increase from 0.39±0.311 to 0.79±0.105 g/cm2 (P<0.05). One patient had fever reaction after first pamidronate infusion but controlled with standard antipyretic therapy, and do not recur in later treatments. Conclusions OI has

  2. Serum microRNA is a promising biomarker for osteogenesis imperfecta.

    Science.gov (United States)

    Wang, Ziqiang; Lu, Yanqin; Zhang, Xiumei; Ren, Xiuzhi; Wang, Yanzhou; Li, Zhiliang; Xu, Chao; Han, Jinxiang

    2012-05-01

    The purpose of our study was to screen preliminary differential expression bone-related microRNAs (miRNAs) in serum of patients with osteogenesis imperfacta and to clarify whether serum microRNA is a promising biomarker for osteogenesis imperfecta. geNorm and several other programes were performed to select suitable reference genes for quantitative detection of serum miRNAs from 6 candidate control genes. With geometric averaging of selected reference genes as a normalization factor, fluorescence-based quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to detect expression levels of more than 100 bone-related miRNAs obtained by means of miRanda, Targetscan and Pictar software calculations and reading the literature. Through analysis of expression stability and pairwise variations, all 6 candidate reference genes had a stable expression level in serum of 8 healthy controls and 8 patients with different characrteristics, and the optimal number of reference genes for normalization was 4 (snRNAU6, miR-92a, miR-16, and Let-7a). For further validation, the expression stability of 4 reference genes remained steady in serum of another 8 healthy controls and 16 patients with osteogenesis imperfecta (M osteogenesis imperfecta patients compared with 8 healthy controls. In conclusion, we identified snRNAU6, miR-92a, miR-16, and Let-7a as an internal reference gene group for qRT-PCR normalization and screening results revealed that there existed many differential expression bone-related miRNAs in serum of patients with osteogenesis imperfecta compared with healthy controls, and that these miRNAs had potential to be biomarkers for serologic tests and diagnosis of osteogenesis imperfecta with analysis of bioinformation.

  3. Femoral artery thrombosis after internal fixation of a transverse acetabular fracture in a patient with osteogenesis imperfecta type I

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    Morgan Steven J

    2008-01-01

    Full Text Available Abstract Osteogenesis imperfecta is a genetic disorder characterized by increased susceptibility to fractures and vascular injuries due to connective tissue fragility. In this case report, we present a patient with osteogenesis imperfecta type I who sustained a transverse fracture of the right acetabulum while transferring from bed to chair. The fracture was repaired through an ilioinguinal approach. During the surgery, an iatrogenic injury to the femoral artery and vein occurred. This intraoperative complication was salvaged by immediate vascular repair. We discuss the possible causes of iatrogenic vascular injuries in patients with osteogenesis imperfecta. Orthopaedic surgeons should be aware of this potentially devastating complication in this particular patient cohort.

  4. Childhood Osteoporosis and Presentation of Two Cases with Osteogenesis Imperfecta Type V / Osteoporoza V Otroški Dobi in Predstavitev Dveh Bolnikov Z Osteogenesis Imperfecta Tipa V

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    Bratanic Nina

    2015-03-01

    Full Text Available Uvod. Osteogenesis imperfecta (OI je vzročno heterogena bolezen, katere značilnost je osteoporoza v otroštvu. Pri vseh opisanih bolnikih s podtipom OI tipa V je vzrok bolezni ista mutacija c.-14C>T gena IFITM5. Kljub temu med bolniki obstaja izrazita fenotipska variabilnost v klinični sliki, toda opisan je le dober odgovor na zdravljenje z bisfosfonati.

  5. What is new in genetics and osteogenesis imperfecta classification?

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    Eugênia R. Valadares

    2014-12-01

    Full Text Available OBJECTIVE: Literature review of new genes related to osteogenesis imperfecta (OI and update of its classification. SOURCES: Literature review in the PubMed and OMIM databases, followed by selection of relevant references. SUMMARY OF THE FINDINGS: In 1979, Sillence et al. developed a classification of OI subtypes based on clinical features and disease severity: OI type I, mild, common, with blue sclera; OI type II, perinatal lethal form; OI type III, severe and progressively deforming, with normal sclera; and OI type IV, moderate severity with normal sclera. Approximately 90% of individuals with OI are heterozygous for mutations in the COL1A1 and COL1A2 genes, with dominant pattern of inheritance or sporadic mutations. After 2006, mutations were identified in the CRTAP, FKBP10, LEPRE1, PLOD2, PPIB, SERPINF1, SERPINH1, SP7, WNT1, BMP1, and TMEM38B genes, associated with recessive OI and mutation in the IFITM5 gene associated with dominant OI. Mutations in PLS3 were recently identified in families with osteoporosis and fractures, with X-linked inheritance pattern. In addition to the genetic complexity of the molecular basis of OI, extensive phenotypic variability resulting from individual loci has also been documented. CONCLUSIONS: Considering the discovery of new genes and limited genotype-phenotype correlation, the use of next-generation sequencing tools has become useful in molecular studies of OI cases. The recommendation of the Nosology Group of the International Society of Skeletal Dysplasias is to maintain the classification of Sillence as the prototypical form, universally accepted to classify the degree of severity in OI, while maintaining it free from direct molecular reference.

  6. Animal models of osteogenesis imperfecta: applications in clinical research

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    Enderli TA

    2016-09-01

    Full Text Available Tanya A Enderli, Stephanie R Burtch, Jara N Templet, Alessandra Carriero Department of Biomedical Engineering, Florida Institute of Technology, Melbourne, FL, USA Abstract: Osteogenesis imperfecta (OI, commonly known as brittle bone disease, is a genetic disease characterized by extreme bone fragility and consequent skeletal deformities. This connective tissue disorder is caused by mutations in the quality and quantity of the collagen that in turn affect the overall mechanical integrity of the bone, increasing its vulnerability to fracture. Animal models of the disease have played a critical role in the understanding of the pathology and causes of OI and in the investigation of a broad range of clinical therapies for the disease. Currently, at least 20 animal models have been officially recognized to represent the phenotype and biochemistry of the 17 different types of OI in humans. These include mice, dogs, and fish. Here, we describe each of the animal models and the type of OI they represent, and present their application in clinical research for treatments of OI, such as drug therapies (ie, bisphosphonates and sclerostin and mechanical (ie, vibrational loading. In the future, different dosages and lengths of treatment need to be further investigated on different animal models of OI using potentially promising treatments, such as cellular and chaperone therapies. A combination of therapies may also offer a viable treatment regime to improve bone quality and reduce fragility in animals before being introduced into clinical trials for OI patients. Keywords: OI, brittle bone, clinical research, mouse, dog, zebrafish

  7. Osteogenesis imperfecta: recent findings shed new light on this once well-understood condition.

    Science.gov (United States)

    Basel, Donald; Steiner, Robert D

    2009-06-01

    Osteogenesis imperfecta is a systemic heritable disorder of connective tissue whose cardinal manifestation is bone fragility. In approximately 90% of individuals with osteogenesis imperfecta, mutations in either of the genes encoding the pro-alpha1 or pro-alpha2 chains of type I collagen (COL1A1 or COL1A2) can be identified. Of those without collagen mutations, a number of them will have mutations involving the enzyme complex responsible for posttranslational hydroxylation of the position 3 proline residue of COL1A1. Two of the genes encoding proteins involved in that enzyme complex, LEPRE1 and cartilage-associated protein, when mutated have been shown to cause autosomal recessive osteogenesis imperfecta, which has a moderate to severe clinical phenotype, often indistinguishable from osteogenesis imperfecta types II or III. Mutations in COL1A1 or COL1A2 which result in an abnormal protein still capable of forming a triple helix cause a more severe phenotype than mutations that lead to decreased collagen production as a result of the dominant negative effect mediated by continuous protein turnover. The current standard of care includes a multidisciplinary approach with surgical intervention when necessary, proactive physiotherapy, and consideration for the use of bisphosphonates all in attempts to improve quality of life.

  8. MRI and CT features of hyperplastic callus in osteogenesis imperfecta tarda

    Energy Technology Data Exchange (ETDEWEB)

    Dobrocky, I. [Diagnostic Center Meidling, Vienna (Austria); Seidl, G. [Diagnostic Center Meidling, Vienna (Austria)]|[Universitaetsklinik fuer Radiodiagnostik, Vienna (Austria); Grill, F. [Orthopaedisches Spital Wien Speising, Vienna (Austria)

    1999-05-01

    We describe the MRI and CT findings of hyperplastic callus formation simulating a tumour of pelvis in patient with osteogenesis imperfecta tarda. Possible differential diagnoses and the impact of different imaging techniques on the correct diagnosis are discussed. (orig.) With 3 figs., 5 refs.

  9. Osteogenesis imperfecta : profiles of motor development as assessed by a postal questionnaire

    NARCIS (Netherlands)

    Engelbert, RHH; Uiterwaal, CSPM; Gulmans, VAM; Pruijs, HEH; Helders, PJM

    2000-01-01

    This study was performed to achieve more detailed information regarding the age and sequence in the development of motor milestones in the different types of osteogenesis imperfecta (OI). The parents of 98 patients with a diagnosis of OI were sent a questionnaire regarding the age at which patients

  10. Percutaneous vertebroplasty in the treatment of vertebral body compression fracture secondary to osteogenesis imperfecta

    Energy Technology Data Exchange (ETDEWEB)

    Rami, Parag M.; Heatwole, Eric V.; Boorstein, Jeffrey M. [Center for Vascular and Interventional Radiology, St. Vincent Mercy Medical Center, Toledo, OH (United States); McGraw, Kevin J. [Riverside Methodist Hospital, Columbus, OH (United States)

    2002-03-01

    Percutaneous vertebroplasty, a minimally invasive interventional radiological procedure, has recently been used effectively for the treatment of symptomatic vertebral body compression fractures. Primary indications for vertebroplasty include osteoporotic compression fracture, osteolytic vertebral metastasis and myeloma, and vertebral hemangioma. We present a case and extend the indication of percutaneous vertebroplasty in a patient with a vertebral body compression fracture secondary to osteogenesis imperfecta. (orig.)

  11. Children with Osteogenesis Imperfecta and Their Daily Living. Handicap Research Group Report No. 4.

    Science.gov (United States)

    Brodin, Jane

    The study examined aspects of daily living of Swedish children with osteogenesis imperfecta, a mineral deficiency in the skeleton which results in stunted growth and frequent fractures. A questionnaire was administered to 24 families with children under the age of 18 and 3 families were interviewed. The study found the families in great need of…

  12. Osteogenesis imperfecta in childhood : effects of spondylodesis on functional ability, ambulation and perceived competence

    NARCIS (Netherlands)

    Tolboom, N; Cats, EA; Helders, PJM; Pruijs, JEH; Engelbert, RHH

    2004-01-01

    We studied the effects of spondylodesis on spinal curvature, functional outcome, level of ambulation and perceived competence in 11 children with osteogenesis imperfecta (OI). Mean age at surgical intervention was 13.1 years (SD 2.5 years) and follow-up amounted to 3.4 years (SD 2.3 years). Spinal c

  13. Three Preschool Children with Osteogenesis Imperfecta--Interviews with Parents. Handicap Research Group Report No. 5.

    Science.gov (United States)

    Brodin, Jane; Millde, Kristina

    The report describes three preschool Swedish children with osteogenesis imperfecta (brittle bones) and the psychosocial support families require from society. Introductory sections explain the condition, review international research on brittle bones, consider the life situation of children with brittle bones, and examine societal support for…

  14. Atypical femoral fracture in an osteogenesis imperfecta patient successfully treated with teriparatide

    DEFF Research Database (Denmark)

    Holm, Jakob; Eiken, Pia; Hyldstrup, Lars;

    2014-01-01

    OBJECTIVE: We report a case of a successfully healed atypical femoral fracture (AFF) following treatment with teriparatide in a patient with osteogenesis imperfecta (OI). To our knowledge, no successful treatment of AFFs with teriparatide in this subpopulation has ever been described. METHODS...

  15. Efficacy and safety of bisphosponate therapy in children with osteogenesis imperfecta: a systematic review

    NARCIS (Netherlands)

    Rijks, Ester B G; Bongers, B.C.; Vlemmix, MJG; Boot, A.M.; van Dijk, ATH; Sakkers, RJB; van Brussel, M

    2015-01-01

    Background/Aims: To systematically assess contemporary knowledge regarding the effectiveness and safety of bisphosphonates (BPs) in children with osteogenesis imperfecta (OI). Methods: PubMed/MEDLINE, Embase, and Cochrane were searched for eligible articles up to June 2014. Studies eligible for incl

  16. Osteogénesis imperfecta con manifestaciones en el periodo neonatal Neonatal Presentation of Osteogenesis Imperfecta

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    Gilberto Rodríguez-Herrera

    2009-04-01

    and given genetic counseling to parents. The osteogenesis imperfecta has a genetic background that affects connective tissue integrity, associated with collagen synthesis mutations, being dominant or recessive autosomic inheritance. In the majority of cases, diagnosis of IO is easy on the basis of clinical and radiological findings; for this reason must be important to emphasize on bone structure studies, because patients may develop cystic, dense or fragile changes. This case presents a patient who has osteogenesis imperfecta type II; we pretend to discuss the differences between Ol’s types.

  17. Unilateral spinal anaesthesia in a patient with Osteogenesis Imperfecta with a lower leg fracture: a case report.

    Science.gov (United States)

    Baranovic, Senka; Lubina, Ivan Zvonimir; Vlahovic, Tomislav; Bakota, Bore; Maldini, Branka

    2013-09-01

    Osteogenesis Imperfecta is a rare, genetically determined disease with several possible complications in anaesthesia. Anaesthesiologists therefore pay special attention to the treatment of patients suffering from Osteogenesis Imperfecta since they commonly suffer from a difficult airway and intraoperative positioning difficulties. We report here the case of unilateral spinal anaesthesia in a patient suffering from Osteogenesis Imperfecta type I. A 28-year-old patient diagnosed with Osteogenesis Imperfecta type I was admitted to the hospital due to lower leg fracture requiring surgical treatment. The patient had blue sclerae, triangular-shaped face, macroglossia, scoliosis of thoracic and lumbar parts of the spine, pectus carinatum and thrombocytopenia. Upon the correction of thrombocytopenia, unilateral spinal anaesthesia with hyperbaric levobupivacain was chosen in order to avoid possible complications typical for general anaesthesia. Consequently, unilateral spinal anaesthesia with a customized local anesthetic could be consdered as a safe anesthetic method for such patients.

  18. Osteogenesis imperfecta in childhood: MR imaging of basilar impression

    Energy Technology Data Exchange (ETDEWEB)

    Janus, G.J.M. E-mail: janus@knmg.nl; Engelbert, R.H.H.; Beek, E.; Gooskens, R.H.J.M.; Pruijs, J.E.H

    2003-07-01

    Objective: To determine on radiographs the presence of Basilar Impression (BI) in children with Osteogenesis Imperfecta (OI). To confirm this sign and altered geometrical relationships of the craniocervical junction in course of time with magnetic resonance imaging (MRI). Methods and patients: In a cohort study of 130 patients with OI (OI type I: 85; OI type III: 21; OI type IV: 24) lateral radiographs of the skull and cervical spine were made in a standardised way. MRI scans were performed when BI was suspected based upon protrusion of the odontoid above Chamberlain's line. Intracranial abnormalities as well as the basal angle were described. Neurological examination was performed in patients with conclusive BI at MRI-scan. Results and discussion: In eight patients BI could be confirmed by MRI-scan. None of the children had or developed in time neurological symptoms or signs. Follow up of BI by MRI scans was done in seven patients (mean: 5 years; range: 2-6 years). No alteration of intracranial findings were seen at subsequent investigation, although in one child Chamberlain's line increased from 8 (first MRI) to 15 mm (last MRI). BI can be diagnosed by radiographs but in the extreme osteoporotic bone and altered anatomy of the craniocervical junction of children with OI MRI is preferable. As intracranial pathology can be demonstrated by MRI, also a relation can be laid to possible neurological symptoms and signs at clinical examination. Conclusion: In our cohort study no alteration of the intracranial contents was seen at subsequent MRI scans. Although anatomic deformations exist in BI, no neurological symptoms or signs were present in our study and no operative reconstruction had to be performed. Periodical MRI-scan has not been of influence on the clinical decision making process. At the moment we perform a MRI-scan if BI is suspected at lateral skull radiographs. The MRI images serve as reference findings to anticipate on possible future symptoms and

  19. Osteogenesis imperfecta: the audiological phenotype lacks correlation with the genotype

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    Swinnen Freya KR

    2011-12-01

    Full Text Available Abstract Background Osteogenesis Imperfecta (OI is a heritable connective tissue disorder mainly caused by mutations in the genes COL1A1 and COL1A2 and is associated with hearing loss in approximately half of the cases. The hearing impairment usually starts between the second and fourth decade of life as a conductive hearing loss, frequently evolving to mixed hearing loss thereafter. A minority of patients develop pure sensorineural hearing loss. The interindividual variability in the audiological characteristics of the hearing loss is unexplained. Methods With the purpose of evaluating inter- and intrafamilial variability, hearing was thorougly examined in 184 OI patients (type I: 154; type III: 4; type IV: 26, aged 3-89 years, with a mutation in either COL1A1 or COL1A2 and originating from 89 different families. Due to the adult onset of hearing loss in OI, correlations between the presence and/or characteristics of the hearing loss and the underlying mutation were investigated in a subsample of 114 OI patients from 64 different families who were older than 40 years of age or had developed hearing loss before the age of 40. Results Hearing loss was diagnosed in 48.4% of the total sample of OI ears with increasing prevalence in the older age groups. The predominant type was a mixed hearing loss (27.5%. A minority presented a pure conductive (8.4% or pure sensorineural (12.5% loss. In the subsample of 114 OI subjects, no association was found between the nature of the mutation in COL1A1 or COL1A2 genes and the occurrence, type or severity of hearing loss. Relatives originating from the same family differed in audiological features, which may partially be attributed to their dissimilar age. Conclusions Our study confirms that hearing loss in OI shows a strong intrafamilial variability. Additional modifications in other genes are assumed to be responsible for the expression of hearing loss in OI.

  20. Severe osteogenesis imperfecta in cyclophilin B-deficient mice.

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    Jae Won Choi

    2009-12-01

    Full Text Available 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.

  1. Osteogenesis imperfecta and clubfoot—a rare combination

    Science.gov (United States)

    Persiani, Pietro; Ranaldi, Filippo Maria; Martini, Lorena; Zambrano, Anna; Celli, Mauro; D’Eufemia, Patrizia; Villani, Ciro

    2016-01-01

    Abstract Background: Osteogenesis imperfecta (OI) is a rare congenital genetic osteodystrophy, which has a prevalence of 1:20,000. OI is caused by the mutation of the COL1A1/COL1A2 genes, leading to a deficit of quality and/or quantity in the synthesis of procollagen-α type 1. Seven different forms of diverse clinical entity have been classified by Sillence and Glorieux, although, recently, up to 11 forms characterized by different genetic mutations have been recognized. Patients with OI suffer from extreme bone fragility and osteoporosis, which often predisposes them to frequent fractures. This paper presents the case of a child with OI type IV who, at birth, was also diagnosed with a severe clubfoot (congenital talipes equinovarus) grade III. Patient's mother also suffers from OI type IV. Methods: The treatment was started by placing femoro-podalic corrective casts, according to the Ponseti method, but some unexpected problems occurred during this treatment. When the patient was 3 months of age, we decided to correct the clubfoot before the time limit planned, performing a bilateral posteromedial surgical release. Results: Three weeks after surgery the casts were removed and replaced with bilateral Spica cast-like braces. On the 6th postoperative week, the patient began wearing Bebax corrective shoes, after 1 year ambidextrous orthopedic shoes. Now, he is 2 years old and has started to walk properly without any orthesis. Conclusion: In the presence of an orthopedic pathology associated with OI, it is recommended to manage the patient according to the underlying pathology, always considering the bone fragility associated with OI. The final surgical treatment to correct the clubfoot can be done earlier, if necessary. In our opinion, this uncommon association between OI and clubfoot is non-syndromic. This means that the two congenital diseases are not necessarily included in a singular uncommon genetic syndrome, but the clubfoot was caused by multifactorial causes

  2. DENTINOGENESIS IMPERFEC TA WITH OSTEOGENESIS IMPERFECTA: A CASE REPORT

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    Jesudass

    2015-03-01

    Full Text Available Dentinogegesis imperfecta (DI represents a group of hereditary conditions that are characterized by abnormal dentin formation. These conditions are genetically and clinically heterogenous and can affect only the teeth or can be associated with the condition Osteogegesis imperfecta . The Osteogegesis imperfecta (OI or the disease of fragile bones is a hereditary pathology affecting different tissues especially the bone. The teeth of DI cases wear more easily and excessively and also more susceptible to dental caries compa red to normal teeth. Early prosthodontic rehabilitation can prevent or delay the wear as well as loss of teeth in DI. Herewith, we present case report of 10yr old boy with discolored, severely attrited permanent teeth with sinus openings. A long with system ic abnormalities like blue sclera, bow legs, protruded sternum. The case was diagnosed as Dentinogegesis imperfecta type I and discussed in this case report.

  3. A rare presentation of a child with osteogenesis imperfecta and congenital laryngomalacia for herniotomy

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    Roshith Chandran

    2011-01-01

    Full Text Available Sometimes anaesthesiologists come across rare congenital anomalies in their practice. The inherent complications associated with the disorder necessitate tailor-made approaches for providing anaesthesia to even seemingly simple surgical interventions. Here, we share our experience of anaesthesia management of an infant with congenital laryngomalacia and recently diagnosed osteogenesis imperfecta type 1 who had presented to us with an acute abdomen for a semi-emergency herniotomy.

  4. Orthopaedic complications of osteogenesis imperfecta; Les complications orthopediques de l'osteogenese imparfaite

    Energy Technology Data Exchange (ETDEWEB)

    Azrak, S.; Ksyar, R.; Ben Rais, N. [hOpital Ibn Sina, CHU de Rabat-Sale, Service de Medecine Nucleaire, Rabat-Sale (Morocco)

    2009-12-15

    Osteogenesis imperfecta is a genetic disease characterized by bone frailty. It is generally caused by an abnormal production of collagen, which is the main fibrous protein of the bone. Collagen is also present in the skin, tendons, the sclera of the eye and dentin. The most frequent manifestation of osteogenesis imperfecta is the occurrence of multiple fractures without major trauma. Severity and timing of the attack varies widely: some patients sustain a significant number of fractures during early childhood which may have a serious impact on growth, while others will have some fractures separated by a few years. In all cases, the bone strength improves in adulthood. The bone fractures cause pain and bone deformities sometimes result in a smaller size. Scoliosis is frequent and associated with painful vertebral collapses. We present a case of osteogenesis imperfecta in a 40-year-old adult and we describe the various orthopaedic complications of the disease, stressing the role of bone scintigraphy in the diagnosis and monitoring of these complications. (authors)

  5. ER stress-mediated apoptosis in a new mouse model of osteogenesis imperfecta.

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    Thomas S Lisse

    2008-02-01

    Full Text Available Osteogenesis imperfecta is an inherited disorder characterized by increased bone fragility, fractures, and osteoporosis, and most cases are caused by mutations affecting the type I collagen genes. Here, we describe a new mouse model for Osteogenesis imperfecta termed Aga2 (abnormal gait 2 that was isolated from the Munich N-ethyl-N-nitrosourea mutagenesis program and exhibited phenotypic variability, including reduced bone mass, multiple fractures, and early lethality. The causal gene was mapped to Chromosome 11 by linkage analysis, and a C-terminal frameshift mutation was identified in the Col1a1 (procollagen type I, alpha 1 gene as the cause of the disorder. Aga2 heterozygous animals had markedly increased bone turnover and a disrupted native collagen network. Further studies showed that abnormal proalpha1(I chains accumulated intracellularly in Aga2/+ dermal fibroblasts and were poorly secreted extracellularly. This was associated with the induction of an endoplasmic reticulum stress-specific unfolded protein response involving upregulation of BiP, Hsp47, and Gadd153 with caspases-12 and -3 activation and apoptosis of osteoblasts both in vitro and in vivo. These studies resulted in the identification of a new model for Osteogenesis imperfecta, and identified a role for intracellular modulation of the endoplasmic reticulum stress-associated unfolded protein response machinery toward osteoblast apoptosis during the pathogenesis of disease.

  6. Immunocytochemical detection of dentin matrix proteins in primary teeth from patients with dentinogenesis imperfecta associated with osteogenesis imperfecta.

    Science.gov (United States)

    Orsini, G; Majorana, A; Mazzoni, A; Putignano, A; Falconi, M; Polimeni, A; Breschi, L

    2014-12-01

    Dentinogenesis imperfecta determines structural alterations of the collagen structure still not completely elucidated. Immunohistochemical 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 (DMP)-1 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. Immunolabeling 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 ultrastructural alterations in dentin obtained from patients affected by DGI-I, supported by immunocytochemical assays of different collagenous and non-collagenous proteins.

  7. Immunocytochemical detection of dentin matrix proteins in primary teeth from patients with dentinogenesis imperfecta associated with osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    G. Orsini

    2014-10-01

    Full Text Available Dentinogenesis imperfecta determines structural alterations of the collagen structure still not completely elucidated. Immunohistochemical 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 (DMP-1 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. Immunolabeling 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 ultrastructural alterations in dentin obtained from patients affected by DGI-I, supported by immunocytochemical assays of different collagenous and non-collagenous proteins.

  8. Phase angle and World Health Organization criteria for the assessment of nutritional status in children with osteogenesis imperfecta

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    Vicky Nogueira Pileggi

    Full Text Available Abstract Objective: To compare the phase angle of patients with osteogenesis imperfecta treated at a tertiary university hospital with patients in a control group of healthy children, and to assess the nutritional status of these patients through the body mass index proposed by the World Health Organization. Methods: Cross-sectional study carried out in a university hospital that included seven patients with osteogenesis imperfecta and a control group of 17 healthy children of the same gender and age. Weight and height were measured and bioelectrical impedance was performed. Subsequently, the phase angle was calculated based on resistance and reactance values. Results: The phase angle of the group of children with osteogenesis imperfecta was significantly lower than that of the control group (p<0.05. The body mass index criterion for age of the World Health Organization showed no difference between groups. Conclusions: Children with osteogenesis imperfecta have a nutritional risk detected by the phase angle, which is a useful tool for nutritional screening. The calculation result could help in the diet therapy of patients with osteogenesis imperfecta.

  9. Phase angle and World Health Organization criteria for the assessment of nutritional status in children with osteogenesis imperfecta

    Science.gov (United States)

    Pileggi, Vicky Nogueira; Scalize, Antonio Rodolpho Hakime; Camelo, José Simon

    2016-01-01

    Abstract Objective: To compare the phase angle of patients with osteogenesis imperfecta treated at a tertiary university hospital with patients in a control group of healthy children, and to assess the nutritional status of these patients through the body mass index proposed by the World Health Organization. Methods: Cross-sectional study carried out in a university hospital that included seven patients with osteogenesis imperfecta and a control group of 17 healthy children of the same gender and age. Weight and height were measured and bioelectrical impedance was performed. Subsequently, the phase angle was calculated based on resistance and reactance values. Results: The phase angle of the group of children with osteogenesis imperfecta was significantly lower than that of the control group (p<0.05). The body mass index criterion for age of the World Health Organization showed no difference between groups. Conclusions: Children with osteogenesis imperfecta have a nutritional risk detected by the phase angle, which is a useful tool for nutritional screening. The calculation result could help in the diet therapy of patients with osteogenesis imperfecta. PMID:27102998

  10. Osteogénesis imperfecta en una gatita de 2 meses - Osteogenesis imperfect in a kitten 2 months

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    Rodríguez, O

    2012-01-01

    Full Text Available ResumenLa ostegénesis imperfecta es una enfermedad congénita. Normalmente es causada por un gen que produce el colágeno tipo I, fundamental para el desarrollo del hueso.SummaryOsteogenesis imperfecta is a congenital disorder. It is normally caused by the gene that produces type I collagen, which is responsible for bone formation.

  11. Swellings over the Limbs as the Earliest Feature in a Patient with Osteogenesis Imperfecta Type V

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    Ali Al Kaissi

    2014-01-01

    Full Text Available Swellings over the upper and lower limbs were encountered in a one-year-old child. Skeletal survey showed a constellation of distinctive radiographic abnormalities of osteoporosis, hyperplastic callus and ossification of the interosseous membrane of the forearm, femora, and to lesser extent the tibiae. Neither wormian bones of the skull nor dentinogenesis imperfecta was present. Genetic tests revealed absence of mutation in COL1A1 or COL1A2 genes, respectively. The overall phenotypic features were consistent with the diagnosis of osteogenesis imperfecta type V (OI-V. The aim of this paper is to distinguish between swellings because of intrinsic bone disorders and these due to child physical abuse.

  12. Genetics Home Reference: dentinogenesis imperfecta

    Science.gov (United States)

    ... abnormalities. Type I occurs in people who have osteogenesis imperfecta , a genetic condition in which bones are brittle ... Dentinogenesis imperfecta type I occurs as part of osteogenesis imperfecta , which is caused by mutations in one of ...

  13. SUCCESSFUL USE OF THE PONSETI METHOD IN THE TREATMENT OF FOUR CHILDREN WITH CLUBFOOT ASSOCIATED WITH OSTEOGENESIS IMPERFECTA TYPE I

    Directory of Open Access Journals (Sweden)

    Валерий Федорович Бландинский

    2014-06-01

    Full Text Available Conservative treatment of congenital clubfoot deformity in osteogenesis imperfecta is very challenging because the high risk of pathological fracture. There is little to no data of such cases hadn’t been found to be described in the literature. We present a child with osteogenesis imperfect and clubfoot deformity, who had been previously inefficiently treated with plaster casts and developed pathological fractures of the tibia. The use of Ponseti method allowed us to completely correct the deformity and avoid complications.

  14. Effect of osteogenesis imperfecta mutations in tropocollagen molecule on strength of biomimetic tropocollagen-hydroxyapatite nanocomposites

    Science.gov (United States)

    Dubey, Devendra K.; Tomar, Vikas

    2010-01-01

    Osteogenesis Imperfecta (OI) is a genetic disorder that affects cellular synthesis of Type-I collagen fibrils and causes extreme bone fragility. This study reports the effects of OI mutations in Tropocollagen (TC) molecules on strength of model Tropocollagen-Hydroxyapatite biomaterials with two different mineral [hydroxyapatite (HAP)] distributions using three dimensional atomistic simulations. Results show that the effect of TC mutations on the strength of TC-HAP biomaterials is insignificant. Instead, change in mineral distribution showed significant impact on the overall strength of TC-HAP biomaterials. Study suggests that TC mutations manifest themselves by changing the mineral distribution during hydroxyapatite growth and nucleation period.

  15. [Bilateral quadriceps rupture in a patient with osteogenesis imperfecta. A case report].

    Science.gov (United States)

    Salcedo-Dueñas, Jesús Alejandro; Torres Castro, Carlos; Estrada Gómez, José Andrés; Algarín Reyes, José Antonio; Bello González, Alejandro

    2009-01-01

    We present the case of a 24-year-old patient with bilateral quadriceps rupture and history of type I congenital osteogenesis imperfecta diagnosed clinically and with ultrasound. Bilateral quadriceps tenoplasty was performed with an anterior approach and without any complications. The patient was discharged with bilateral neoprene knee-guards. The sutures were removed at the 21-day follow-up visit, rehabilitation was started at six weeks and the patient was doing well at the 2- and 3-month follow-up visits. Timely management and early rehabilitation contribute to decrease the risk of sequelae despite the poor functional prognosis.

  16. Investigation of the Human Disease Osteogenesis Imperfecta: A Research-Based Introduction to Concepts and Skills in Biomolecular Analysis

    Science.gov (United States)

    Mate, Karen; Sim, Alistair; Weidenhofer, Judith; Milward, Liz; Scott, Judith

    2013-01-01

    A blended approach encompassing problem-based learning (PBL) and structured inquiry was used in this laboratory exercise based on the congenital disease Osteogenesis imperfecta (OI), to introduce commonly used techniques in biomolecular analysis within a clinical context. During a series of PBL sessions students were presented with several…

  17. Lethal osteogenesis imperfecta congenita and a 300 base pair gene deletion for an α1(I)-like collagen.

    NARCIS (Netherlands)

    F.M. Pope; K.S.E. Cheah (Kathryn); A.C. Nicholls; A.B. Price; F.G. Grosveld (Frank)

    1984-01-01

    textabstractBroad boned lethal osteogenesis imperfecta is a severely crippling disease of unknown cause. By means of recombinant DNA technology a 300 base pair deletion in an alpha 1(I)-like collagen gene was detected in six patients and four complete parent-child groups including patients with this

  18. Pyridinium cross-links in bone of patients with osteogenesis imperfecta: Evidence of a normal intrafibrillar collagen packing

    NARCIS (Netherlands)

    Bank, R.A.; Tekoppele, J.M.; Janus, G.J.M.; Wassen, M.H.M.; Pruijs, H.E.H.; Sluijs, H.A.H. van der; Sakkers, R.J.B.

    2000-01-01

    The brittleness of bone in patients with osteogenesis imperfecta (OI) has been attributed to an aberrant collagen network. However, the role of collagen in the loss of tissue integrity has not been well established. To gain an insight into the biochemistry and structure of the collagen network, the

  19. Hyperplastic callus formation in osteogenesis imperfecta type V mimicking osteosarcoma: 4-year follow-up with resolution

    Energy Technology Data Exchange (ETDEWEB)

    Vieira, R.L.V.; Amaral, D.T. [Federal University of Sao Paulo, Department of Radiology, Sao Paulo (Brazil); Jesus-Garcia, Filho R. [Federal University of Sao Paulo, Department of Orthopedic Surgery, Sao Paulo (Brazil); Saraiva, G. [Federal University of Sao Paulo, Department of Endocrinology, Sao Paulo (Brazil); Fernandes, A.R.C. [University of California San Diego, Department of MSK Radiology, San Diego, CA (United States); Resnick, D.

    2006-06-15

    We report a case of hyperplastic callus formation that occurred in both femurs in a patient with type V osteogenesis imperfecta (OI), with 4-year follow-up and resolution. The clinical, histological and imaging aspects of this condition are discussed. Recognition of the hyperplastic callus formation in this particular type of OI is important in order to avoid misdiagnosis. (orig.)

  20. Complete Remodeling after Conservative Treatment of a Severely Angulated Odontoid Fracture in a Patient with Osteogenesis Imperfecta : A Case Report

    NARCIS (Netherlands)

    Colo, Dino; Schlösser, Tom P C; Oostenbroek, Hubert J.; Castelein, RM

    2015-01-01

    Study Design. Case report. Objective. This is the first case report describing successful healing and remodeling of a traumatic odontoid fracture that was dislocated and severely angulated in a patient with osteogenesis imperfecta who was treated conservatively. Summary of Background Data. Osteogene

  1. Spontaneous and simultaneous bilateral rupture of the quadriceps tendon in a patient with osteogenesis imperfecta: a case report.

    Science.gov (United States)

    Figueroa, David; Calvo, Rafael; Vaisman, Alex

    2006-03-01

    Bilateral rupture of the quadriceps tendon is an uncommon and serious injury that usually occurs in middle aged to elderly patients. It is frequently associated with chronic metabolic disorders like diabetes, hyperparathyroidism, gout, chronic renal failure or the chronic use of steroids. We report a case of spontaneous bilateral rupture of the quadriceps tendon in a patient with osteogenesis imperfecta.

  2. CRTAP mutations in lethal and severe osteogenesis imperfecta: the importance of combining biochemical and molecular genetic analysis.

    NARCIS (Netherlands)

    Dijk, F.S. Van; Nesbitt, I.M.; Nikkels, P.G.J.; Dalton, A.; Bongers, E.M.H.F.; Kamp, J.M. van de; Hilhorst-Hofstee, Y.; Hollander, N.S. den; Lachmeijer, A.M.; Marcelis, C.L.M.; Tan-Sindhunata, G.M.; Rijn, R.R. van; Meijers-Heijboer, H.; Cobben, J.M.; Pals, G.

    2009-01-01

    Autosomal recessive lethal and severe osteogenesis imperfecta (OI) is caused by the deficiency of cartilage-associated protein (CRTAP) and prolyl-3-hydroxylase 1 (P3H1) because of CRTAP and LEPRE1 mutations. We analyzed five families in which 10 individuals had a clinical diagnosis of lethal and sev

  3. CRTAP mutations in lethal and severe osteogenesis imperfecta : the importance of combining biochemical and molecular genetic analysis

    NARCIS (Netherlands)

    Van Dijk, Fleur S.; Nesbitt, Isabel M.; Nikkels, Peter G. J.; Dalton, Ann; Bongers, Ernie M. H. F.; de Kamp, Jiddeke M. van; Hilhorst-Hofstee, Yvonne; Den Hollander, Nicolette S.; Lachmeijer, Augusta M. A.; Marcelis, Carlo L.; Tan-Sindhunata, Gita M. B.; van Rijn, Rick R.; Meijers-Heijboer, Hanne; Cobben, Jan M.; Pals, Gerard

    2009-01-01

    Autosomal recessive lethal and severe osteogenesis imperfecta (OI) is caused by the deficiency of cartilage-associated protein (CRTAP) and prolyl-3-hydroxylase 1 (P3H1) because of CRTAP and LEPRE1 mutations. We analyzed five families in which 10 individuals had a clinical diagnosis of lethal and sev

  4. Tomographic imaging of collagen-mineral interaction: implications for osteogenesis imperfecta.

    Science.gov (United States)

    Landis, W J

    1995-01-01

    The novel method of high voltage electron microscopic tomography (3D) has been applied for the first time to examine ultrastructural features and spatial relations between collagen fibrils and mineral crystals in a mouse mutant (oim/oim) which replicates a moderate to severe form of osteogenesis imperfecta. The animal produces collagen consisting of the alpha1(I) homotrimer and has a brittle calcified skeleton. Three-dimensional image reconstructions of the Achilles tendons, which were found to mineralize in the mutant mice, revealed that their composite crystals were different in their structural appearance and spatial association with collagen compared to that determined in normal calcified tissues. These results indicate that the nature of the organic matrix of a mineralizing tissue critically influences the formation, structure, and location of the constituent mineral and, further, the data are interpreted as suggesting that the unusual structural and organizational interaction between mineral and collagen underlies the inherent brittleness and weakness of calcification in this model of osteogenesis imperfecta.

  5. Deficient expression of the small proteoglycan decorin in a case of severe/lethal osteogenesis imperfecta

    Energy Technology Data Exchange (ETDEWEB)

    Dyne, K.M.; Valli, M.; Forlino, A.; Cetta, G. [Univ. of Pavia (Italy); Mottes, M. [Univ. of Verona (Italy); Kresse, H. [Univ. of Muenster (Germany)

    1996-05-03

    In osteogenesis imperfecta (OI) the effects of mutations in type I collagen genes generally reflect their nature and localization. Unrelated individuals sharing identical mutations present, in general, similar clinical phenotypes. However, in some such cases the clinical phenotype differs. This variable clinical expression could be the result of abnormalities in other connective tissue proteins. Since decorin is a component of connective tissue, binds to type I collagen fibrils and plays a role in matrix assembly, we studied decorin production in skin fibroblasts from OI patients. Cultured fibroblasts from one patient with extremely severe osteogenesis imperfecta (classified as type II/III) who has an {alpha}1(I)gly415ser mutation were found to secrete barely detectable amounts of decorin into culture medium. Western blotting using antibodies raised against decorin confirmed the reduction of the decorin core protein and Northern blot analysis showed decorin mRNA levels below the limit of detection. Cells from a patient, with a less severe phenotype, bearing a mutation in the same position of the triple helix ({alpha}1(1)gly415) expressed decorin normally. The different clinical phenotypes could be due to the differing genetic backgrounds of the patients, so it is tempting to conclude that in our most severely affected patient, the absence of decorin aggravates the clinical phenotype. 34 refs., 4 figs., 1 tab.

  6. Developmental charts for children with osteogenesis imperfecta, type I (body height, body weight and BMI).

    Science.gov (United States)

    Graff, Krzysztof; Syczewska, Malgorzata

    2017-03-01

    Osteogenesis imperfecta (OI) is a rare genetic disorder of type I collagen. Type I is the most common, which is called a non-deforming type of OI, as in this condition, there are no major bone deformities. This type is characterised by blue sclera and vertebral fractures, leading to mild scoliosis. The body height of these patients is regarded as normal, or only slightly reduced, but there are no data proving this in the literature. The aim of this study is the preparation of the developmental charts of children with OI type I. The anthropometric data of 117 patients with osteogenesis imperfecta were used in this study (61 boys and 56 girls). All measurements were pooled together into one database (823 measurements in total). To overcome the problem of the limited number of data being available in certain age classes and gender groups, the method called reverse transformation was used. The body height of the youngest children, aged 2 and 3 years, is less than that of their healthy peers. Children between 4 and 7 years old catch up slightly, but at later ages, development slows down, and in adults, the median body height shows an SDS of -2.7.

  7. Next-generation sequencing of common osteogenesis imperfecta-related genes in clinical practice

    Science.gov (United States)

    Árvai, Kristóf; Horváth, Péter; Balla, Bernadett; Tobiás, Bálint; Kató, Karina; Kirschner, Gyöngyi; Klujber, Valéria; Lakatos, Péter; Kósa, János P.

    2016-01-01

    Next generation sequencing (NGS) is a rapidly developing area in genetics. Utilizing this technology in the management of disorders with complex genetic background and not recurrent mutation hot spots can be extremely useful. In this study, we applied NGS, namely semiconductor sequencing to determine the most significant osteogenesis imperfecta-related genetic variants in the clinical practice. We selected genes coding collagen type I alpha-1 and-2 (COL1A1, COL1A2) which are responsible for more than 90% of all cases. CRTAP and LEPRE1/P3H1 genes involved in the background of the recessive forms with relatively high frequency (type VII and VIII) represent less than 10% of the disease. In our six patients (1–41 years), we identified 23 different variants. We found a total of 14 single nucleotide variants (SNV) in COL1A1 and COL1A2, 5 in CRTAP and 4 in LEPRE1. Two novel and two already well-established pathogenic SNVs have been identified. Among the newly recognized mutations, one results in an amino acid change and one of them is a stop codon. We have shown that a new full-scale cost-effective NGS method can be developed and utilized to supplement diagnostic process of osteogenesis imperfecta with molecular genetic data in clinical practice. PMID:27335225

  8. Hereditary osteogenesis imperfecta in a Chinese family%遗传性成骨不全家系分析

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

      目的探讨遗传性成骨不全(osteogenesis imperfecta,OI)一家系特征。方法2011年6月对河南安阳OI家系进行问卷调查、专科检查,搜集临床资料,绘制家系图谱,分析临床特点和遗传方式。结果该家系4代40人,患者10例,现存活患者7例,其中男5例,女2例。存活7例均存在骨折病史、骨骼畸形、蓝色巩膜、牙齿发育异常,3例听力受损,3例出现骨折愈合不良。结论该家系临床诊断符合Sillence I型成骨不全,遗传方式为常染色体显性遗传。%Objective To study the features of hereditary osteogenesis imperfecta in a Chinese family tree. Methods Hereditary osteogenesis imperfecta in a family of Anyang City, Henan Province, China, was investigated with questionnaire. The family underwent examination in our department and its clinical data were collected. An atlas was plotted for the family. The clinical features of hereditary osteogenesis imperfecta and its hereditary mode were analyzed. Results There were 40 members including 4 generations in the family. Of the 10 members with hereditary osteogenesis imperfecta, 7 were survivors (5 males and 2 females) with a history of fracture, bone deformity, blue sclera and teeth dysplasia, 3 had hearing impairment and 3 had poor fracture healing. Conclusion The clinical diagnosis of hereditary osteogenesis imperfecta in the family is consistent with Sillence I osteogenesis imperfecta with autosomal dominant inheritance as its hereditary mode.

  9. Standardized X-ray reports of the spine in osteogenesis imperfecta; Standard zur Befundung von Roentgenaufnahmen der Wirbelsaeule bei Patienten mit Osteogenesis imperfecta

    Energy Technology Data Exchange (ETDEWEB)

    Koerber, Friederike; Demant, A.W.; Koerber, S. [Universitaetsklinikum Koeln (Germany). Kinderradiologie, Inst. und Poliklinik fuer Radiologische Diagnostik; Semler, O.; Schoenau, E. [Universitaetsklinikum Koeln (Germany). Osteologie, Klinik und Poliklinik fuer Allgemeine Kinderheilkunde; Lackner, K.J. [Universitaetsklinikum Koeln (Germany). Inst. und Poliklinik fuer Radiologische Diagnostik

    2011-05-15

    Purpose: In this study we present a standard for radiological reports in patients with osteogenesis imperfecta (OI). The parameters can be used to describe X-rays of the lateral spine and give an impartial description of anatomical structures during a treatment with bisphosphonates. Material and Methods: In this retrospective analysis we included 48 patients with OI (31 female, 17 male [1.5 months - 19 years, mean age 9.0 years]). Lateral spine X-rays were analyzed by 2 radiologists before and during treatment. The parameters of the standardized report are degree of kyphoscoliosis, compression of single vertebrae, predominant type of vertebral deformities and extent of vertebral compression (score 1 - 5). Results: There was no clear trend in the change of compression of single vertebrae. Some vertebrae with ventral compression showed an upgrowth to vertebrae with harmonic compression. Other deformities showed only marginal changes. In 26 patients the kyphoscoliosis improved (mean 10 degrees), in 36 patients the thoracic vertebrae compression increased and in 30 patients the vertebral height in the lumbar spine increased. The improvement of vertebral height was 1 point in the thoracic and lumbar spine. Conclusion: We propose a standardized report of X-rays of the lateral spine in patients with OI with quantitative and semiquantitative parameters using morphological criteria. These include compression of single vertebrae, degree of kyphoscoliosis, vertebral deformities and the severity of vertebral compression in the thoracic and lumbar spine. (orig.)

  10. Intravitreal bevacizumab for treatment of choroidal neovascularization associated with osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Pukhraj Rishi

    2012-01-01

    Full Text Available A 12-year-old girl, diagnosed of osteogenesis imperfecta, presented with sudden visual loss in the left eye. Investigations revealed an active choroidal neovascular membrane. She underwent treatment with intravitreal Bevacizumab (1.25 mg/0.05 ml. Follow-up at 1 month revealed the development of lacquer crack running through the macula, underlying the fovea. The patient received two re-treatments at 1-month intervals, following which the choroidal neovascularization (CNV regressed completely. However, further progression of lacquer cracks was noted. At the last follow-up, 6 months following the last injection, the fundus remained stable and vision was maintained at 20/200. Considering the natural history of the disease and the increased risk of rupture of the Bruch′s membrane in such eyes, the possible complication of a lacquer crack developing must be borne in mind, before initiating treatment.

  11. In vivo laser confocal microscopy findings of a cornea with osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Kobayashi A

    2014-02-01

    Full Text Available Akira Kobayashi, Tomomi Higashide, Hideaki Yokogawa, Natsuko Yamazaki, Toshinori Masaki, Kazuhisa Sugiyama Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan Objective: To report the in vivo laser confocal microscopy findings of a cornea with osteogenesis imperfecta (OI with special attention to the abnormality of Bowman's layer and sub-Bowman's fibrous structures (K-structures. Patients and methods: Two patients (67-year-old male and his 26-year-old son with OI type I were included in this study. Slit lamp biomicroscopic and in vivo laser confocal microscopic examinations were performed for both patients. Central corneal thickness and central endothelial cell density were also measured. Results: Although the corneas looked clear with normal endothelial density for both eyes in both patients, they were quite thin (386 µm oculus dexter (OD (the right eye and 384 µm oculus sinister (OS (the left eye in the father and 430 µm OD and 425 µm OS in the son. In both patients, slit lamp biomicroscopic and in vivo laser confocal microscopic examination showed similar results. Anterior corneal mosaics produced by rubbing the eyelid under fluorescein were completely absent in both eyes. In vivo laser confocal microscopy revealed an absent or atrophic Bowman's layer; a trace of a presumed Bowman's layer and/or basement membrane was barely visible with high intensity. Additionally, K-structures were completely absent in both eyes. Conclusion: The absence of K-structures and fluorescein anterior corneal mosaics strongly suggested an abnormality of Bowman's layer in these OI patients. Keywords: osteogenesis imperfecta, K-structure, confocal microscopy, Bowman's layer

  12. Increased intra-cortical porosity reduces bone stiffness and strength in pediatric patients with osteogenesis imperfecta.

    Science.gov (United States)

    Vardakastani, V; Saletti, D; Skalli, W; Marry, P; Allain, J M; Adam, C

    2014-12-01

    Osteogenesis imperfecta (OI) is a heritable disease occurring in one out of every 20,000 births. Although it is known that Type I collagen mutation in OI leads to increased bone fragility, the mechanism of this increased susceptibility to fracture is not clear. The aim of this study was to assess the microstructure of cortical bone fragments from patients with osteogenesis imperfecta (OI) using polarized light microscopy, and to correlate microstructural observations with the results of previously performed mechanical compression tests on bone from the same source. Specimens of cortical bone were harvested from the lower limbs of three (3) OI patients at the time of surgery, and were divided into two groups. Group 1 had been subjected to previous micro-mechanical compression testing, while Group 2 had not been subjected to any prior testing. Polarized light microscopy revealed disorganized bone collagen architecture as has been previously observed, as well as a large increase in the areal porosity of the bone compared to typical values for healthy cortical bone, with large (several hundred micron sized), asymmetrical pores. Importantly, the areal porosity of the OI bone samples in Group 1 appears to correlate strongly with their previously measured apparent Young's modulus and compressive strength. Taken together with prior nanoindentation studies on OI bone tissue, the results of this study suggest that increased intra-cortical porosity is responsible for the reduction in macroscopic mechanical properties of OI cortical bone, and therefore that in vivo imaging modalities with resolutions of ~100 μm or less could potentially be used to non-invasively assess bone strength in OI patients. Although the number of subjects in this study is small, these results highlight the importance of further studies in OI bone by groups with access to human OI tissue in order to clarify the relationship between increased porosity and reduced macroscopic mechanical integrity.

  13. Comparison of Calcitonin and Pamidronate Treatments in Children with Osteogenesis Imperfecta

    Directory of Open Access Journals (Sweden)

    Neslihan Onenli Mungan

    2013-08-01

    Full Text Available Purpose: The main objective of this study was to compare the treatments of calcitonin and pamidronate by clinical, biochemical, and radiological findings in children with osteogenesis imperfecta and evaluate the efficiency of pamidronate treatment. Patients and methods: A total of 12 patients, aged 41±38 (1-120 months were studied. Group 1 was consisted of six patients who had received intranasal calcitonin at a dosage of 4-6 U/kg three times a week before switching to pamidronate treatment. Group 2 was also consisted of six patients who had received only pamidronate infusion at a dosage of 0.5-2 mg/kg every two months. Results: Annual fracture rates decreased from 2.72 ± 0.80 to 0.40 ± 0.70 (p0.05, and from -3.08 ± -0.61 to -2.29 ± -0.56 in pamidronate group. The difference between the Z-scores of bone mineral density after calcitonin and pamidronate treatments was statistically significant (p<0.05. The Z-scores of pre (-3.44 ± -0.96 and post (-2.47 ± -0.60 pamidronate treatments of whole 12 patients were significantly different (p<0.001. Conclusion: Pamidronate was significantly more effective in reducing pain, annual fracture rate, and increasing bone mineral density and mobility than calcitonin without any severe adverse effects even in the neonatal period and severe forms of osteogenesis imperfecta. [Cukurova Med J 2013; 38(4.000: 667-674

  14. Osteogenesis imperfecta type V: clinical and radiographic manifestations in mutation confirmed patients.

    Science.gov (United States)

    Kim, Ok-Hwa; Jin, Dong-Kyu; Kosaki, Keisuke; Kim, Jung-Wook; Cho, Sung Yoon; Yoo, Won Joon; Choi, In Ho; Nishimura, Gen; Ikegawa, Shiro; Cho, Tae-Joon

    2013-08-01

    Osteogenesis imperfecta (OI) type V is a specific OI phenotype with interosseous membrane calcification of the forearm and hyperplastic callus formation as typical features. The causative gene mutation for OI type V has been recently discovered. The purpose of this report is to review the clinical and radiographic characteristics of mutation confirmed OI type V in detail. Sixteen (nine familial and seven sporadic) patients were enrolled in the study. Blue sclera and dentinogenesis imperfecta were not evident in any patient. However, hypodontia in the permanent teeth, ectopic eruption, and short roots in molars were additionally observed in 11 patients. Of the radiographic abnormalities, cortical thickening and bony excrescence of interosseous margin of the ulna was the most common finding, followed by overgrowth of the olecranon and/or coronoid process of the ulna. Slender ribs and sloping of the posterior ribs with or without fractures were also a consistent finding. Hyperplastic callus was detected in 75% of patients and was commonly encountered at the femur. Heterotopic ossification in the muscles and tendon insertion sites were noted in four patients, which resulted in bony ankylosis or contracture of joints. The current study confirms common clinical and radiographic findings of OI type V and reports additional phenotypic information. These observations provide clues to recognize OI type V more promptly and guide to direct targeted molecular study. © 2013 Wiley Periodicals, Inc.

  15. What every clinical geneticist should know about testing for osteogenesis imperfecta in suspected child abuse cases.

    Science.gov (United States)

    Pepin, Melanie G; Byers, Peter H

    2015-12-01

    Non-accidental injury (NAI) is a major medical concern in the United States. One of the challenges in evaluation of children with unexplained fractures is that genetic forms of bone fragility are one of the differential diagnoses. Infants who present with fractures with mild forms of osteogenesis imperfecta (OI) (OI type I or OI type IV), the most common genetic form of bone disease leading to fractures might be missed if clinical evaluation alone is used to make the diagnosis. Diagnostic clinical features (blue sclera, dentinogenesis imperfecta, Wormian bones on X-rays or positive family history) may not be present or apparent at the age of evaluation. The evaluating clinician faces the decision about whether genetic testing is necessary in certain NAI cases. In this review, we outline clinical presentations of mild OI and review the history of genetic testing for OI in the NAI versus OI setting. We summarize our data of molecular testing in the Collagen Diagnostic Laboratory (CDL) from 2008 to 2014 where NAI was noted on the request for DNA sequencing of COL1A1 and COL1A2. We provide recommendations for molecular testing in the NAI versus OI setting. First, DNA sequencing of COL1A1, COL1A2, and IFITM5 simultaneously and duplication/deletion testing is recommended. If a causative variant is not identified, in the absence of a pathologic clinical phenotype, no additional gene testing is indicated. If a VUS is found, parental segregation studies are recommended.

  16. Genetic epidemiology, prevalence, and genotype–phenotype correlations in the Swedish population with osteogenesis imperfecta

    Science.gov (United States)

    Lindahl, Katarina; Åström, Eva; Rubin, Carl-Johan; Grigelioniene, Giedre; Malmgren, Barbro; Ljunggren, Östen; Kindmark, Andreas

    2015-01-01

    Osteogenesis imperfecta (OI) is a rare hereditary bone fragility disorder, caused by collagen I mutations in 90% of cases. There are no comprehensive genotype–phenotype studies on >100 families outside North America, and no population-based studies determining the genetic epidemiology of OI. Here, detailed clinical phenotypes were recorded, and the COL1A1 and COL1A2 genes were analyzed in 164 Swedish OI families (223 individuals). Averages for bone mineral density (BMD), height and yearly fracture rate were calculated and related to OI and mutation type. N-terminal helical mutations in both the α1- and α2-chains were associated with the absence of dentinogenesis imperfecta (P95% of the complete Swedish pediatric OI population. The prevalence of OI types I, III, and IV was 5.16, 0.89, and 1.35/100 000, respectively (7.40/100 000 overall), corresponding to what has been estimated but not unequivocally proven in any population. Collagen I mutation analysis was performed in the family of 97% of known cases, with causative mutations found in 87%. Qualitative mutations caused 32% of OI type I. The data reported here may be helpful to predict phenotype, and describes for the first time the genetic epidemiology in >95% of an entire OI population. PMID:25944380

  17. Genetic epidemiology, prevalence, and genotype-phenotype correlations in the Swedish population with osteogenesis imperfecta.

    Science.gov (United States)

    Lindahl, Katarina; Åström, Eva; Rubin, Carl-Johan; Grigelioniene, Giedre; Malmgren, Barbro; Ljunggren, Östen; Kindmark, Andreas

    2015-08-01

    Osteogenesis imperfecta (OI) is a rare hereditary bone fragility disorder, caused by collagen I mutations in 90% of cases. There are no comprehensive genotype-phenotype studies on >100 families outside North America, and no population-based studies determining the genetic epidemiology of OI. Here, detailed clinical phenotypes were recorded, and the COL1A1 and COL1A2 genes were analyzed in 164 Swedish OI families (223 individuals). Averages for bone mineral density (BMD), height and yearly fracture rate were calculated and related to OI and mutation type. N-terminal helical mutations in both the α1- and α2-chains were associated with the absence of dentinogenesis imperfecta (P95% of the complete Swedish pediatric OI population. The prevalence of OI types I, III, and IV was 5.16, 0.89, and 1.35/100 000, respectively (7.40/100 000 overall), corresponding to what has been estimated but not unequivocally proven in any population. Collagen I mutation analysis was performed in the family of 97% of known cases, with causative mutations found in 87%. Qualitative mutations caused 32% of OI type I. The data reported here may be helpful to predict phenotype, and describes for the first time the genetic epidemiology in >95% of an entire OI population.

  18. A Case Report for a Complex Denture Case on a Special Care Patient with Osteogenesis Imperfecta.

    Science.gov (United States)

    Sawyer, Colin; Drysdale, David

    2015-05-01

    This case report presents a patient with Dentogenesis Imperfecta (DI) associated with Osteogenesis Imperfecta (OI) and its subsequent dental manifestations. The patient in this report (see Figure 1) has spent his life living with his disability type III OI (also known as brittle bone disease) and its degenerative affects. The patient is independent and enjoys his social life but felt his existing dentures were having an adverse effect on the quality of his life. The patient attended Dorset County Hospitals Special Care Dentistry and on clinical examination it was noted the patient was partially dentate with a class III malocclusion and brownish discoloration of the remaining teeth caused by enamel hypoplasia. Treatment for this patient would entail making a maxillary complete denture and a mandibular partial chrome denture, normally quite simple tasks but due to the DI and its dental manifestations, the treatment would be complicated. This case demonstrates how a complex case treated by a collaborative dental team using their different skills and knowledge can lead to a successful and rewarding treatment for both patient and team.

  19. Anestesia venosa total em paciente portador de Osteogênesis imperfecta: relato de caso Anestesia venosa total en paciente portador de Osteogénesis imperfecta: relato de caso Total intravenous anesthesia in Osteogenesis imperfecta patient: case report

    OpenAIRE

    José Francisco Nunes Pereira das Neves; Roberto Silva Sant'Anna; João Rosa de Almeida; Rodrigo Machado Saldanha; Marcos Gonçalves Magalhães

    2004-01-01

    JUSTIFICATIVA E OBJETIVOS: A Osteogênesis Imperfecta é uma doença genética rara do tecido conjuntivo, com prevalência de 1/10000, que primariamente envolve a ossificação endocondral, resultando em ossos frágeis, múltiplas fraturas e deformidades esqueléticas. O objetivo desse artigo foi relatar um caso de paciente portador de Osteogenesis Imperfecta, submetido à anestesia venosa total para tratamento cirúrgico de fratura de fêmur. RELATO DO CASO: Paciente do sexo masculino, 15 anos, 41 kg, 14...

  20. Гематурия у ребенка с несовершенным остеогенезом (osteogenesis imperfecta)

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    Gupte Tejashri; Iyer V; Damle S; Malik N; Halbe A

    2011-01-01

    Osteogenesis imperfecta is an inherited disorder of the connective tissue. The extreme bone fragility seen in patients suffering from osteogenesis imperfecta pose a series of problems with regard to behavior management and rendering of quality dental treatment. Presented here a case of a four year old child suffering from osteogenesis imperfecta.

  1. Advance of Genetics Studies on Osteogenesis Imperfecta%成骨不全遗传学研究进展

    Institute of Scientific and Technical Information of China (English)

    任旋; 陈慧; 张秀德

    2012-01-01

    成骨不全是一种遗传性全身结缔组织疾病,以编码Ⅰ型胶原蛋白的基因(COL1A1和COL1A2)突变为主要致病机制,导致Ⅰ型胶原合成障碍,骨脆性增加.本文就成骨不全的临床分型、分子遗传学及治疗进展做一综述.%Osteogenesis imperfecta is a hereditary systemic connective tissue diseases with encoding type I collagen gene ( COL1A1 and COL1A2 ) mutation as the main pathogenic mechanism, which brings about type I collagen disorders, bone fragility. In this paper, we briefly reviewed the clinical type of osteogenesis imperfecta, the advances in molecular genetics and the treatment for the disease.

  2. Eleven years of experience with bisphosphonate plus alfacalcidol treatment in a man with osteogenesis imperfecta type I

    Directory of Open Access Journals (Sweden)

    Iwamoto J

    2012-12-01

    Full Text Available Jun Iwamoto,1 Yoshihiro Sato,2 Mitsuyoshi Uzawa,3 Hideo Matsumoto11Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, 2Department of Neurology, Mitate Hospital, Fukuoka, 3Department of Orthopaedic Surgery, Keiyu Orthopaedic Hospital, Gunma, JapanAbstract: We report the 11-year follow-up of a man with osteogenesis imperfecta type I who was treated with bisphosphonates and alfacalcidol. A 36-year-old Japanese man with osteogenesis imperfecta type I who had frequently experienced painful fragility fractures consulted our clinic because of chronic back pain. The patient had multiple morphometric vertebral fractures and a low bone mineral density (BMD at the lumbar spine. The patient was treated with cyclical etidronate 200 mg, for 2 weeks every 3 months, plus alfacalcidol 1 µg daily, for 2 years; and alendronate 5 mg daily or 35 mg weekly, plus alfacalcidol 1 µg daily for 9 years. After 11 years of treatment, BMD at the lumbar spine increased by 6.4%, following a 20.3% reduction in serum alkaline phosphatase. Serum calcium, phosphorus, and intact parathyroid hormone levels remained within the normal ranges. Three clinical fractures occurred at two ribs and the metacarpus, and two morphometric vertebral fractures occurred at the thoracic spine during the 11-year treatment period, but the patient experienced no adverse effects. Thus, the present case report shows the long-term outcome and safety of bisphosphonate plus alfacalcidol treatment in a man with osteogenesis imperfecta type I.Keywords: etidronate, alendronate, fragility fracture, bone mineral density, osteogenesis imperfecta

  3. Osteogenesis Imperfecta Model Peptides: Incorporation of Residues Replacing Gly within a Triple Helix Achieved by Renucleation and Local Flexibility

    OpenAIRE

    Xiao, Jianxi; Madhan, Balaraman; Li, Yingjie; Brodsky, Barbara; Baum, Jean

    2011-01-01

    Missense mutations, which replace one Gly with a larger residue in the repeating sequence of the type I collagen triple helix, lead to the hereditary bone disorder osteogenesis imperfecta (OI). Previous studies suggest that these mutations may interfere with triple-helix folding. NMR was used to investigate triple-helix formation in a series of model peptides where the residue replacing Gly, as well as the local sequence environment, was varied. NMR measurement of translational diffusion coef...

  4. A deletion in the gene encoding sphingomyelin phosphodiesterase 3 (Smpd3) results in osteogenesis and dentinogenesis imperfecta in the mouse.

    Science.gov (United States)

    Aubin, Isabelle; Adams, Carolyn P; Opsahl, Sibylle; Septier, Dominique; Bishop, Colin E; Auge, Nathalie; Salvayre, Robert; Negre-Salvayre, Anne; Goldberg, Michel; Guénet, Jean-Louis; Poirier, Christophe

    2005-08-01

    The mouse mutation fragilitas ossium (fro) leads to a syndrome of severe osteogenesis and dentinogenesis imperfecta with no detectable collagen defect. Positional cloning of the locus identified a deletion in the gene encoding neutral sphingomyelin phosphodiesterase 3 (Smpd3) that led to complete loss of enzymatic activity. Our knowledge of SMPD3 function is consistent with the pathology observed in mutant mice and provides new insight into human pathologies.

  5. Reduced diaphyseal strength associated with high intracortical vascular porosity within long bones of children with osteogenesis imperfecta.

    Science.gov (United States)

    Albert, Carolyne; Jameson, John; Smith, Peter; Harris, Gerald

    2014-09-01

    Osteogenesis imperfecta is a genetic disorder resulting in bone fragility. The mechanisms behind this fragility are not well understood. In addition to characteristic bone mass deficiencies, research suggests that bone material properties are compromised in individuals with this disorder. However, little data exists regarding bone properties beyond the microstructural scale in individuals with this disorder. Specimens were obtained from long bone diaphyses of nine children with osteogenesis imperfecta during routine osteotomy procedures. Small rectangular beams, oriented longitudinally and transversely to the diaphyseal axis, were machined from these specimens and elastic modulus, yield strength, and maximum strength were measured in three-point bending. Intracortical vascular porosity, bone volume fraction, osteocyte lacuna density, and volumetric tissue mineral density were determined by synchrotron micro-computed tomography, and relationships among these mechanical properties and structural parameters were explored. Modulus and strength were on average 64-68% lower in the transverse vs. longitudinal beams (Pbone volume. Longitudinal properties were associated negatively with porosity (P≤0.006, linear regressions). Mechanical properties, however, were not associated with osteocyte lacuna density or volumetric tissue mineral density (P≥0.167). Bone properties and structural parameters were not associated significantly with donor age (P≥0.225, linear mixed models). This study presents novel data regarding bone material strength in children with osteogenesis imperfecta. Results confirm that these properties are anisotropic. Elevated vascular porosity was observed in most specimens, and this parameter was associated with reduced bone material strength. These results offer insight toward understanding bone fragility and the role of intracortical porosity on the strength of bone tissue in children with osteogenesis imperfecta.

  6. Potential of human fetal chorionic stem cells for the treatment of osteogenesis imperfecta.

    Science.gov (United States)

    Jones, Gemma N; Moschidou, Dafni; Abdulrazzak, Hassan; Kalirai, Bhalraj Singh; Vanleene, Maximilien; Osatis, Suchaya; Shefelbine, Sandra J; Horwood, Nicole J; Marenzana, Massimo; De Coppi, Paolo; Bassett, J H Duncan; Williams, Graham R; Fisk, Nicholas M; Guillot, Pascale V

    2014-02-01

    Osteogenesis imperfecta (OI) is a genetic bone pathology with prenatal onset, characterized by brittle bones in response to abnormal collagen composition. There is presently no cure for OI. We previously showed that human first trimester fetal blood mesenchymal stem cells (MSCs) transplanted into a murine OI model (oim mice) improved the phenotype. However, the clinical use of fetal MSC is constrained by their limited number and low availability. In contrast, human fetal early chorionic stem cells (e-CSC) can be used without ethical restrictions and isolated in high numbers from the placenta during ongoing pregnancy. Here, we show that intraperitoneal injection of e-CSC in oim neonates reduced fractures, increased bone ductility and bone volume (BV), increased the numbers of hypertrophic chondrocytes, and upregulated endogenous genes involved in endochondral and intramembranous ossification. Exogenous cells preferentially homed to long bone epiphyses, expressed osteoblast genes, and produced collagen COL1A2. Together, our data suggest that exogenous cells decrease bone brittleness and BV by directly differentiating to osteoblasts and indirectly stimulating host chondrogenesis and osteogenesis. In conclusion, the placenta is a practical source of stem cells for the treatment of OI.

  7. Bisphosphonates for the prevention of fractures in osteogenesis imperfecta: meta-analysis of placebo-controlled trials.

    Science.gov (United States)

    Hald, Jannie D; Evangelou, Evangelos; Langdahl, Bente L; Ralston, Stuart H

    2015-05-01

    Bisphosphonates are widely used off-label in the treatment of patients with osteogenesis imperfecta (OI) with the intention of reducing the risk of fracture. Although there is strong evidence that bisphosphonates increase bone mineral density in osteogenesis imperfecta, the effects on fracture occurrence have been inconsistent. The aim of this study was to gain a better insight into the effects of bisphosphonate therapy on fracture risk in patients with osteogenesis imperfecta by conducting a meta-analysis of randomized controlled trials in which fractures were a reported endpoint. We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials in which the effects of bisphosphonates on fracture risk in osteogenesis imperfecta were compared with placebo and conducted a meta-analysis of these studies using standard methods. Heterogeneity was assessed using the I2 statistic. Six eligible studies were identified involving 424 subjects with 751 patient-years of follow-up. The proportion of patients who experienced a fracture was not significantly reduced by bisphosphonate therapy (Relative Risk [RR] = 0.83 [95% confidence interval 0.69-1.01], p = 0.06) with no heterogeneity between studies (I2  = 0). The fracture rate was reduced by bisphosphonate treatment when all studies were considered (RR = 0.71 [0.52-0.96], p = 0.02), but with considerable heterogeneity (I2  = 36%) explained by one study where a small number of patients in the placebo group experienced a large number of fractures. When this study was excluded, the effects of bisphosphonates on fracture rate was not significant (RR = 0.79 [0.61-1.02], p = 0.07, I2  = 0%). We conclude that the effects of bisphosphonates on fracture prevention in osteogenesis imperfecta are inconclusive. Adequately powered trials with a fracture endpoint are needed to further investigate the risks and benefits of bisphosphonates in this condition.

  8. A rare case of osteogenesis imperfecta combined with complete tooth loss.

    Science.gov (United States)

    Lu, Yanqin; Zhao, Fei; Ren, Xiuzhi; Li, Zhiliang; Yang, Xiaomeng; Han, Jinxiang

    2014-01-01

    Osteogenesis imperfecta (OI) is a heritable disorder of the connective tissue characterized by blue sclerae, osteoporosis and bone fragility. Dentinogenesis imperfecta type I is commonly seen in OI patients, but other dental impairments, such as tooth agenesis or complete tooth loss, are rarely reported for these patients. Here, we report the case of a 37-year-old female Chinese OI patient who experienced complete tooth loss before puberty. The patient has a family history of OI and her father has a history of tooth loss. She showed obvious OI phenotypes, including a dwarfed stature, blue sclerae, scoliosis, pigeon chest and a history of fractures. Tooth loss began at the age of 6 years and continued until complete tooth loss at 20 years; this occurred in the absence of dental decay, gum disease, accidents or drug usage. Radiological studies revealed osteoporosis of the lower limbs and an underdeveloped scapula. Type I collagen gene analysis identified a known c.2314G>A (p.Gly772Ser) substitution in the COL1A2 gene, which we suggest affects the interaction between type I collagen and extracellular matrix proteins, including cartilage oligomeric matrix protein, phosphophoryn and SPARC (secreted protein acidic and rich in cysteine). In silico prediction indicated a relatively mild effect of the mutation, so it is conceivable that the severity of the clinical phenotype may result from additional mutations in candidate genes responsible for abnormal dental phenotypes in this family. To our knowledge, this is the first report of an OI patient with a phenotype of complete tooth loss at a young age.

  9. AB069. Effect of osteogenesis imperfecta on children and their families

    Science.gov (United States)

    Dung, Vu Chi; Armstrong, Kate; Ngoc, Can Thi Bich; Thao, Bui Phuong; Khanh, Nguyen Ngoc; Trang, Nguyen Thu; Hoan, Nguyen Thi; Dat, Nguyen Phu; Munns, Craig

    2015-01-01

    Osteogenesis imperfecta (OI) is a heterogeneous genetic disorder, with features that include increased bone fragility, pathological fractures, blue sclera, dentinogenesis imperfecta and conductive or mixed hearing loss. Clinical variability is wide from children with few fractures and normal stature to children with multiple fractures, long bone deformity, scoliosis and extreme short stature. Although there is no curative treatment, there are several therapeutic tools capable of improving the course of the condition and patient quality of life. We aim to evaluate the effect of OI on the well-being of children with the disorder and their families through a family-centered questionnaire. Sixty children with OI from the Vietnam National Hospital of Pediatrics and/or their parent(s), who attended the first annual family support group in 2011, completed a child and parent questionnaire. Sixty patients participated, 26 female and 34 male. The median age was 6.0 years [interquartile range (IQR), 0.25-18 years]. Of these, 36 (60%) had dentinogenesis imperfect and 23 (38.3%) had a scoliosis. The median number of fractures was 6.0 (IQR 0-30) and median number of hospitalizations due to OI was 5.0 (IQR 0-30). Among patients of school age, 9 (15%) could not go to school due to OI. Almost all parents (93.7%) worried about school social communication of the patients. Among these parents, 100% fear of inferiority with friends and 98.3% fear of broken bones. Most parents (76.2%) were significantly concerned about their child’s health. The parents’ themselves reported psychological concerns, with feelings of desperation (58.4%), anxiety (81.7%) and depression (56.7%). OI appeared to have a significant deleterious effect on the life of the patients and their families. These data provide a baseline from which to evaluate the effectiveness of interventions to improve the medical and psychological needs of this cohort and their families.

  10. Distinctive tomographic abnormalities of the craniocervical region in a patient with osteogenesis imperfecta type IV B

    Energy Technology Data Exchange (ETDEWEB)

    Kaissi, Ali Al; Klaushofer, Klaus, E-mail: ali.alkaissi@osteologie.a [Ludwig Boltzmann Institute of Osteology, Vienna (Austria); Grill, Franz [Orthopaedic Hospital of Speising, Vienna (Austria). Paediatric Dept.

    2010-07-01

    Osteogenesis imperfecta is a clinically and genetically heterogeneous group of heritable disorders of connective tissue characterized by reduced bone mass (osteopenia) with associated bone fragility. The resulting skeletal manifestations are due to a generalized deficiency in the development of both membranous and endochondral bone and include markedly thin calvarium with delayed closure of the fontanelles and the sutures and excessive Wormian bone formation. Sillence et al. developed a classification system of OI subtypes: OI type I, which is characterised by blue sclerae; perinatal lethal OI type II, also known as congenital OI; OI type III, a progressively deforming subtype with normal sclera; and OI type IV, which is characterized by a normal sclera. Levin et al. have suggested that OI subtypes could be further divided into type A and B based on the absence or presence of dentinogenesis imperfecta. Basilar impression involves the upward (vertical) migration of the odontoid process into the foramen magnum with a depression in the cranium. Basilar impression is a developmental defect and refers to the infolding of the occipital condyles, an elevation of the clivus, and the posterior cranial fossa of the skull. The soft bones of the skull base allow for progressive infolding of the dysplastic clivus and translocation of the odontoid into the posterior fossa. The combination of platybasia and basilar impression can lead to severe distortion of the spinal cord and the anterior brain stem. The specific structures that can be involved include the upper cervical cord, medulla, pons, mid-brain, cerebellum, as well as the vertebrobasilar system. (author)

  11. The sagittal balance of the spine in children and adolescents with osteogenesis imperfecta.

    Science.gov (United States)

    Abelin, Karimane; Vialle, Raphaël; Lenoir, Thibault; Thévenin-Lemoine, Camille; Damsin, Jean-Paul; Forin, Véronique

    2008-12-01

    In severe forms of osteogenesis imperfecta, multiple compression fractures of the spine, as well as vertebral height shortening could be responsible for an increased thoracic kyphosis or a diminished lumbar lordosis. Theses progressive changes in sagittal shapes of the trunk could be responsible for a global sagittal trunk imbalance. We compare the parameters of sagittal spinopelvic balance in young patients with OI to those parameters in a control group of healthy volunteers. Eighteen patients with osteogenesis imperfecta were compared to a cohort of 300 healthy volunteers. A standing lateral radiograph of the spine was obtained in a standardized fashion. The sacral slope, pelvic tilt, pelvic incidence, lumbar lordosis, thoracic kyphosis, T1 and T9 sagittal offset were measured using a computer-assisted method. The variations and reciprocal correlations of all parameters in both groups according to each other were studied. Comparison of angular parameters between OI patients and control group showed an increased T1T12 kyphosis in OI patients. T1 and T9 sagittal offset was positive in OI patients and negative in control group. This statistically significant difference among sagittal offsets in both groups indicated that OI patients had a global sagittal balance of the trunk displaced anteriorly when compared to the normal population. Reciprocal correlations between angular parameters in OI patients showed a strong correlation between lumbar lordosis (L1L5 and L1S1) and sacral slope. The T9 sagittal offset was also strongly correlated with pelvic tilt. Pelvic incidence was correlated with L1S1 lordosis, T1 sagittal offset and pelvic tilt. In OI patients, the T1T12 thoracic kyphosis was statistically higher than in control group and was not correlated with other shape (LL) or pelvic (SS, PT or PI) parameters. Because isolated T1T12 kyphosis increase without T4T12 significant modification, we suggest that vertebral deformations worsen in OI patients at the upper part

  12. Robust physical methods that enrich genomic regions identical by descent for linkage studies: confirmation of a locus for osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Cohen Nadine

    2009-03-01

    Full Text Available Abstract Background The monogenic disease osteogenesis imperfecta (OI is due to single mutations in either of the collagen genes ColA1 or ColA2, but within the same family a given mutation is accompanied by a wide range of disease severity. Although this phenotypic variability implies the existence of modifier gene variants, genome wide scanning of DNA from OI patients has not been reported. Promising genome wide marker-independent physical methods for identifying disease-related loci have lacked robustness for widespread applicability. Therefore we sought to improve these methods and demonstrate their performance to identify known and novel loci relevant to OI. Results We have improved methods for enriching regions of identity-by-descent (IBD shared between related, afflicted individuals. The extent of enrichment exceeds 10- to 50-fold for some loci. The efficiency of the new process is shown by confirmation of the identification of the Col1A2 locus in osteogenesis imperfecta patients from Amish families. Moreover the analysis revealed additional candidate linkage loci that may harbour modifier genes for OI; a locus on chromosome 1q includes COX-2, a gene implicated in osteogenesis. Conclusion Technology for physical enrichment of IBD loci is now robust and applicable for finding genes for monogenic diseases and genes for complex diseases. The data support the further investigation of genetic loci other than collagen gene loci to identify genes affecting the clinical expression of osteogenesis imperfecta. The discrimination of IBD mapping will be enhanced when the IBD enrichment procedure is coupled with deep resequencing.

  13. Multiparametric Classification of Skin from Osteogenesis Imperfecta Patients and Controls by Quantitative Magnetic Resonance Microimaging.

    Directory of Open Access Journals (Sweden)

    Beth G Ashinsky

    Full Text Available The purpose of this study is to evaluate the ability of quantitative magnetic resonance imaging (MRI to discriminate between skin biopsies from individuals with osteogenesis imperfecta (OI and skin biopsies from individuals without OI. Skin biopsies from nine controls (unaffected and nine OI patients were imaged to generate maps of five separate MR parameters, T1, T2, km, MTR and ADC. Parameter values were calculated over the dermal region and used for univariate and multiparametric classification analysis. A substantial degree of overlap of individual MR parameters was observed between control and OI groups, which limited the sensitivity and specificity of univariate classification. Classification accuracies ranging between 39% and 67% were found depending on the variable of investigation, with T2 yielding the best accuracy of 67%. When several MR parameters were considered simultaneously in a multivariate analysis, the classification accuracies improved up to 89% for specific combinations, including the combination of T2 and km. These results indicate that multiparametric classification by quantitative MRI is able to detect differences between the skin of OI patients and of unaffected individuals, which motivates further study of quantitative MRI for the clinical diagnosis of OI.

  14. A fracture risk assessment model of the femur in children with osteogenesis imperfecta (OI) during gait.

    Science.gov (United States)

    Fritz, Jessica M; Guan, Yabo; Wang, Mei; Smith, Peter A; Harris, Gerald F

    2009-11-01

    Osteogenesis imperfecta (OI) is a heritable bone fragility disorder characterized by skeletal deformities and increased bone fragility. There is currently no established clinical method for quantifying fracture risk in OI patients. This study begins the development of a patient-specific model for femur fracture risk assessment and prediction based on individuals' gait analysis data, bone geometry from imaging and material properties from nanoindentation (Young's modulus=19 GPa, Poisson's ratio=0.3). Finite element models of the femur were developed to assess fracture risk of the femur in a pediatric patient with OI type I. Kinetic data from clinical gait analysis was used to prescribe loading conditions on the femoral head and condyles along with muscle forces on the bone's surface. von Mises stresses were analyzed against a fracture strength of 115 MPa. The patient with OI whose femur was modeled showed no risk of femoral fracture during normal gait. The highest stress levels occurred during the mid-stance and loading responses phases of gait. The location of high stress migrated throughout the femoral diaphysis across the gait cycle. Maximum femoral stress levels occurred during the gait cycle phases associated with the highest loading. The fracture risk (fracture strength/von Mises stress), however, was low. This study provides a relevant method for combining functional activity, material property and analytical methods to improve patient monitoring.

  15. Microstructural and Photoacoustic Infrared Spectroscopic Studies of Human Cortical Bone with Osteogenesis Imperfecta

    Science.gov (United States)

    Gu, Chunju; Katti, Dinesh R.; Katti, Kalpana S.

    2016-04-01

    The molecular basis of bone disease osteogenesis imperfecta (OI) and the mineralization of hydroxyapatite in OI bone have been of significant research interest. To further investigate the mechanism of OI disease and bone mineralization, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy, and x-ray diffraction (XRD) are used in the present study to describe the structural and compositional differences between OI and healthy bone. OI bone exhibits more porous, fibrous features, abnormal collagen fibrils, and abnormal mineral deposits. Likewise, photoacoustic-FTIR experiments indicate an aberrant collagen structure and an altered mineral structure in OI. In contrast, there is neither significant difference in the non-collagenous proteins (NCPs) composition observed nor apparent change in the crystal structure between OI and healthy bone minerals as shown in XRD and energy-dispersive x-ray spectroscopy (EDS) results. This observation indicates that the biomineralization process is more controlled by the bone cells and non-collagenous phosphorylated proteins. The present study also confirms that there is an orientational influence on the stoichiometry of the mineral in OI bone. Also, a larger volume of the hydrated layer in the transverse plane than the longitudinal plane of the mineral crystal structure is proposed. The appearance of a new C-S band in the FTIR spectra in OI bone suggests the substitution of glycine by cysteine in collagen molecules or/and an increased amount of cysteine-rich osteonectin that relates to mineral nucleation and mineral crystal formation.

  16. Micro-CT characterization of human trabecular bone in osteogenesis imperfecta

    Science.gov (United States)

    Jameson, John; Albert, Carolyne; Smith, Peter; Molthen, Robert; Harris, Gerald

    2011-03-01

    Osteogenesis imperfecta (OI) is a genetic syndrome affecting collagen synthesis and assembly. Its symptoms vary widely but commonly include bone fragility, reduced stature, and bone deformity. Because of the small size and paucity of human specimens, there is a lack of biomechanical data for OI bone. Most literature has focused on histomorphometric analyses, which rely on assumptions to extrapolate 3-D properties. In this study, a micro-computed tomography (μCT) system was used to directly measure structural and mineral properties in pediatric OI bone collected during routine surgical procedures. Surface renderings suggested a poorly organized, plate-like orientation. Patients with a history of bone-augmenting drugs exhibited increased bone volume fraction (BV/TV), trabecular number (Tb.N), and connectivity density (Eu.Conn.D). The latter two parameters appeared to be related to OI severity. Structural results were consistently higher than those reported in a previous histomorphometric study, but these differences can be attributed to factors such as specimen collection site, drug therapy, and assumptions associated with histomorphometry. Mineral testing revealed strong correlations with several structural parameters, highlighting the importance of a dual approach in trabecular bone testing. This study reports some of the first quantitative μCT data of human OI bone, and it suggests compelling possibilities for the future of OI bone assessment.

  17. Quantitative second-harmonic generation imaging to detect osteogenesis imperfecta in human skin samples

    Science.gov (United States)

    Adur, J.; Ferreira, A. E.; D'Souza-Li, L.; Pelegati, V. B.; de Thomaz, A. A.; Almeida, D. B.; Baratti, M. O.; Carvalho, H. F.; Cesar, C. L.

    2012-03-01

    Osteogenesis Imperfecta (OI) is a genetic disorder that leads to bone fractures due to mutations in the Col1A1 or Col1A2 genes that affect the primary structure of the collagen I chain with the ultimate outcome in collagen I fibrils that are either reduced in quantity or abnormally organized in the whole body. A quick test screening of the patients would largely reduce the sample number to be studied by the time consuming molecular genetics techniques. For this reason an assessment of the human skin collagen structure by Second Harmonic Generation (SHG) can be used as a screening technique to speed up the correlation of genetics/phenotype/OI types understanding. In the present work we have used quantitative second harmonic generation (SHG) imaging microscopy to investigate the collagen matrix organization of the OI human skin samples comparing with normal control patients. By comparing fibril collagen distribution and spatial organization, we calculated the anisotropy and texture patterns of this structural protein. The analysis of the anisotropy was performed by means of the two-dimensional Discrete Fourier Transform and image pattern analysis with Gray-Level Co-occurrence Matrix (GLCM). From these results, we show that statistically different results are obtained for the normal and disease states of OI.

  18. Gender-dependence of bone structure and properties in adult osteogenesis imperfecta murine model.

    Science.gov (United States)

    Yao, Xiaomei; Carleton, Stephanie M; Kettle, Arin D; Melander, Jennifer; Phillips, Charlotte L; Wang, Yong

    2013-06-01

    Osteogenesis imperfecta (OI) is a dominant skeletal disorder characterized by bone fragility and deformities. Though the oim mouse model has been the most widely studied of the OI models, it has only recently been suggested to exhibit gender-dependent differences in bone mineralization. To characterize the impact of gender on the morphometry/ultra-structure, mechanical properties, and biochemical composition of oim bone on the congenic C57BL/J6 background, 4-month-old oim/oim, +/oim, and wild-type (wt) female and male tibiae were evaluated using micro-computed tomography, three-point bending, and Raman spectroscopy. Dramatic gender differences were evident in both cortical and trabecular bone morphological and geometric parameters. Male mice had inherently more bone and increased moment of inertia than genotype-matched female counterparts with corresponding increases in bone biomechanical strength. The primary influence of gender was structure/geometry in bone growth and mechanical properties, whereas the mineral/matrix composition and hydroxyproline content of bone were influenced primarily by the oim collagen mutation. This study provides evidence of the importance of gender in the evaluation and interpretation of potential therapeutic strategies when using mouse models of OI.

  19. The effect of SERPINF1 in-frame mutations in osteogenesis imperfecta type VI.

    Science.gov (United States)

    Al-Jallad, Hadil; Palomo, Telma; Roughley, Peter; Glorieux, Francis H; McKee, Marc D; Moffatt, Pierre; Rauch, Frank

    2015-07-01

    Osteogenesis imperfecta type VI is caused by mutations in SERPINF1, which codes for pigment-epithelium derived factor (PEDF). Most of the reported SERPINF1 mutations lead to premature termination codons, but three in-frame insertion or deletion mutations have also been reported. It is not clear how such in-frame mutations lead to OI type VI. In the present study we therefore investigated how SERPINF1 in-frame mutations affect the intracellular localization and secretion of PEDF. Skin fibroblasts affected by SERPINF1 in-frame mutations transcribed SERPINF1 at slightly reduced levels but secretion of PEDF was markedly diminished. Two deletions (p.F277del and the deletion of SERPINF1 exon 5) were associated with retention of PEDF in the endoplasmic reticulum and a stress response in osteoblastic cells. A recurrent in-frame duplication of three amino acids (p.Ala91_Ser93dup) appeared to lead to intracellular degradation but no retention in the endoplasmic reticulum or stress response. Immunofluorescence imaging in transiently transfected osteoblastic MC3T3-E1 cells suggested that PEDF affected by in-frame mutations was not transported along the secretory pathway. MC3T3-E1 osteoblasts stably overexpressing SERPINF1 with the p.Ala91_Ser93dup mutation had decreased collagen type I deposition and mineralization. Thus, the assessed homozygous in-frame deletions or insertions lead to retention or degradation within cellular compartments and thereby interfere with PEDF secretion.

  20. Osteogenesis Imperfecta Presented with Vertebral Fractures After Pregnancy and Treatment with Cyclical Etidronate: A Case Report

    Directory of Open Access Journals (Sweden)

    Cengiz Bahadır

    2005-06-01

    Full Text Available Osteogenesis imperfecta(OI is a kongenital skelatal disorder charecterized by low bone mass and increased bone fragility. Fractures due to increased bone fragility occur frequently in childhood and decrease with age. Only a few studies have been reported regarding the teratment of adult patients with OI. Our case was a 27 year old woman with severe back pain occured when she was lifting her baby. The patient had experienced multiple fractures of long bones by her childhood. Compression fractures at thoracal 10 and 12 vertebrae were found on Magnetic Resonance Imaging . Dual energy X-ray absorptiomety(DEXA showed that markedly decreased bone mineral density(BMD both at lumbar spine and femur. The diagnosis of OI type I was based on the findings of blue sclera, antecedent multiple fractures, positive family history and low bone mass. Patient was treated with cyclical etidronate, calcium and Vitamin D over a year. No new fractures were observed during the treatment period. Lomber and proximal femur BMD’s were found to be significantly increased at the end of one year. Our case was treated succesfully with combination of cyclical etidronate, calcium and vitamin D. Etidronate would seem to be available treatment for adult patients with OI. However, the best treatment regimen and the long-term outcomes of etidronate therapy are unknown.

  1. Quantitative changes in human epithelial cancers and osteogenesis imperfecta disease detected using nonlinear multicontrast microscopy

    Science.gov (United States)

    Adur, Javier; Pelegati, Vitor B.; de Thomaz, Andre A.; D'Souza-Li, Lilia; Assunção, Maria do Carmo; Bottcher-Luiz, Fátima; Andrade, Liliana A. L. A.; Cesar, Carlos L.

    2012-08-01

    We show that combined multimodal nonlinear optical (NLO) microscopies, including two-photon excitation fluorescence, second-harmonic generation (SHG), third harmonic generation, and fluorescence lifetime imaging microscopy (FLIM) can be used to detect morphological and metabolic changes associated with stroma and epithelial transformation during the progression of cancer and osteogenesis imperfecta (OI) disease. NLO microscopes provide complementary information about tissue microstructure, showing distinctive patterns for different types of human breast cancer, mucinous ovarian tumors, and skin dermis of patients with OI. Using a set of scoring methods (anisotropy, correlation, uniformity, entropy, and lifetime components), we found significant differences in the content, distribution and organization of collagen fibrils in the stroma of breast and ovary as well as in the dermis of skin. We suggest that our results provide a framework for using NLO techniques as a clinical diagnostic tool for human cancer and OI. We further suggest that the SHG and FLIM metrics described could be applied to other connective or epithelial tissue disorders that are characterized by abnormal cells proliferation and collagen assembly.

  2. Introduction of a new standardized assessment score of spine morphology in osteogenesis imperfecta

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    Koerber, F.; Schulze Uphoff, U.; Koerber, S.; Maintz, D. [Koeln Univ. (Germany). Dept. of Radiology; Schoenau, E.; Semler, O. [Koeln Univ. (Germany). Children' s Hospital

    2012-08-15

    Purpose: Osteogenesis imperfecta (OI) is a rare hereditary disease leading to multiple bone deformities and fractures. In the absence of causal therapy, a symptomatic approach is based on treatment with bisphosphonates and physiotherapy. The clinical and radiological manifestations vary. Therefore, standardization and quantification for an objective comparison, especially during therapy, are required. In this paper, radiological changes of the spine are quantified according to their clinical relevance to define a scoring system that transfers the morphological changes into a single value representing the severity of the disease. Materials and Methods: 268 lateral spine X-rays of 95 patients with OI (median age 5.6 years) were assessed. The findings were classified based on their clinical relevance. Results: The three criteria, vertebral compression, thoracolumbar kyphosis and deformity type, were quantified in a new grading system. Based on this, a 'severity classification' (1 to 5) was defined with implications for diagnostics and treatment. A mathematical formula that takes into account the three criteria and their correlations to clinical relevance, resulting in a 'severity score', was developed. Conclusion: 'Severity classification' and 'severity score' introduce a new concept for a standardized evaluation of spine X-rays in patients with OI. For both scientific and routine purposes, it provides the user with a simple and easy-to-handle tool for assessing and comparing different stages of severity prior to and during therapy with detailed accuracy. (orig.)

  3. Child abuse and osteogenesis imperfecta: how can they be still misdiagnosed? A case report

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    D’Eufemia, Patrizia; Palombaro, Marta; Lodato, Valentina; Zambrano, Anna; Celli, Mauro; Persiani, Pietro; De Bari, Maria Pia; Sangiorgi, Luca

    2012-01-01

    Summary Osteogenesis imperfecta (OI) is a rare hereditary disease caused by mutations in genes coding for type I collagen, resulting in bone fragility. In literature are described forms lethal in perinatal period, forms which are moderate and slight forms where the only sign of disease is osteopenia. Child abuse is an important social and medical problem. Fractures are the second most common presentation after skin lesions and may present specific patterns. The differential diagnosis between slight-moderate forms of OI and child abuse could be very challenging especially when other signs typical of abuse are absent, since both could present with multiple fractures without reasonable explanations. We report a 20 months-old female with a history of 4 fractures occurred between the age of three and eighteen months, brought to authorities’ attention as a suspected child abuse. However when she came to our department physical examination, biochemical tests, total body X-ray and a molecular analysis of DNA led the diagnosis of OI. Thus, a treatment with bisphosphonate and a physical rehabilitation process, according to Vojta method, were started with improvement in bony mineralization, gross motor skills and absence of new fracture. In conclusion our case demonstrates how in any child presenting fractures efforts should be made to consider, besides child abuse, all the other hypothesis even the rarest as OI. PMID:23289038

  4. Ultra-structural defects cause low bone matrix stiffness despite high mineralization in osteogenesis imperfecta mice☆

    Science.gov (United States)

    Vanleene, Maximilien; Porter, Alexandra; Guillot, Pascale-Valerie; Boyde, Alan; Oyen, Michelle; Shefelbine, Sandra

    2012-01-01

    Bone is a complex material with a hierarchical multi-scale organization from the molecule to the organ scale. The genetic bone disease, osteogenesis imperfecta, is primarily caused by mutations in the collagen type I genes, resulting in bone fragility. Because the basis of the disease is molecular with ramifications at the whole bone level, it provides a platform for investigating the relationship between structure, composition, and mechanics throughout the hierarchy. Prior studies have individually shown that OI leads to: 1. increased bone mineralization, 2. decreased elastic modulus, and 3. smaller apatite crystal size. However, these have not been studied together and the mechanism for how mineral structure influences tissue mechanics has not been identified. This lack of understanding inhibits the development of more accurate models and therapies. To address this research gap, we used a mouse model of the disease (oim) to measure these outcomes together in order to propose an underlying mechanism for the changes in properties. Our main finding was that despite increased mineralization, oim bones have lower stiffness that may result from the poorly organized mineral matrix with significantly smaller, highly packed and disoriented apatite crystals. Using a composite framework, we interpret the lower oim bone matrix elasticity observed as the result of a change in the aspect ratio of apatite crystals and a disruption of the crystal connectivity. PMID:22449447

  5. High prevalence of coxa vara in patients with severe osteogenesis imperfecta.

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    Aarabi, Mehdi; Rauch, Frank; Hamdy, Reggie C; Fassier, François

    2006-01-01

    The purpose of this study was to determine the incidence and clinical presentation of coxa vara in 283 patients with osteogenesis imperfecta (OI). The charts and X-rays of 150 girls and 133 boys with OI were reviewed. The patients were classified according to the Sillence classification modified by Glorieux: 94 type I, 90 type IV, 67 type III, 18 type V, 10 type VI, and 4 type VII. The mean age was 9.4 years (range 0.3-23.3). Twenty-nine patients (10.2%) had coxa vara (23 left and 20 right). Fifty-five percent of them were type III, 24% type IV, 13.8% type VI, and 3.4% each of types V and VII. The incidence of coxa vara was 6% in type V, 8% in type IV, 24% in type III, 25% in type VII, and 40% in type VI (P Trendelenburg gait. In conclusion, coxa vara in OI is not rare, especially in severe forms of the disease. Regular clinical and radiologic follow-up is indicated in children with previous femoral rodding and in severely affected children, particularly those with OI type III.

  6. Mechanical and mineral properties of osteogenesis imperfecta human bones at the tissue level.

    Science.gov (United States)

    Imbert, Laurianne; Aurégan, Jean-Charles; Pernelle, Kélig; Hoc, Thierry

    2014-08-01

    Osteogenesis imperfecta (OI) is a genetic disorder characterized by an increase in bone fragility on the macroscopic scale, but few data are available to describe the mechanisms involved on the tissue scale and the possible correlations between these scales. To better understand the effects of OI on the properties of human bone, we studied the mechanical and chemical properties of eight bone samples from children suffering from OI and compared them to the properties of three controls. High-resolution computed tomography, nanoindentation and Raman microspectroscopy were used to assess those properties. A higher tissue mineral density was found for OI bone (1.131 gHA/cm3 vs. 1.032 gHA/cm3, p=0.032), along with a lower Young's modulus (17.6 GPa vs. 20.5 GPa, p=0.024). Obviously, the mutation-induced collagen defects alter the collagen matrix, thereby affecting the mineralization. Raman spectroscopy showed that the mineral-to-matrix ratio was higher in the OI samples, while the crystallinity was lower, suggesting that the mineral crystals were smaller but more abundant in the case of OI. This change in crystal size, distribution and composition contributes to the observed decrease in mechanical strength.

  7. Associação entre artrite idiopática juvenil e osteogenesis imperfecta: relato de caso

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    Blanca Elena Rios Gomes Bica

    2013-12-01

    Full Text Available Os autores relatam o caso de uma paciente de 53 anos que apresenta uma rara associação entre artrite idiopática juvenil (AIJ e osteogenesis imperfecta (OI, com acometimento poliarticular, incluindo a articulação temporomandibular. Apresentam uma revisão da literatura e uma discussão dos aspectos radiológicos do acometimento da referida articulação. Não foram encontrados relatos de casos com semelhante associação de doenças na literatura especializada.

  8. Deep tissue single cell MSC ablation using a fiber laser source to evaluate therapeutic potential in osteogenesis imperfecta

    Science.gov (United States)

    Tehrani, Kayvan F.; Pendleton, Emily G.; Lin, Charles P.; Mortensen, Luke J.

    2016-04-01

    Osteogenesis imperfecta (OI) is a currently uncurable disease where a mutation in collagen type I yields brittle bones. One potential therapy is transplantation of mesenchymal stem cells (MSCs), but controlling and enhancing transplanted cell survival has proven challenging. Therefore, we use a 2- photon imaging system to study individual transplanted cells in the living bone marrow. We ablated cells deep in the bone marrow and observed minimal collateral damage to surrounding tissue. Future work will evaluate the local impact of transplanted MSCs on bone deposition in vivo.

  9. Anesthetic management for combined mitral valve replacement and aortic valve repair in a patient with osteogenesis imperfecta

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    Huang Jiapeng

    2011-01-01

    Full Text Available Osteogenesis imperfecta is a rare disorder of connective tissues and presents multiple challenges, including difficult airway, hyperthermia, coagulopathy and respiratory dysfunction, for anesthesiologists, especially during cardiac surgery. We present anesthetic management of a patient with osteogenesis impertecta during double valve surgery. Dexmedetomidine infusion minimized the risks of malignant hyperthermia. Glidescope and in-line stabilization facilitated endotracheal intubation and protected his oral structures and cervical spine. Transesophageal echocardiography (TEE diagnosed a flail A3 segment and redundant left coronary cusp causing mitral and aortic regurgitation. The mitral valve was replaced and the aortic valve repaired. Coagulopathy was corrected according to comprehensive coagulation analysis. Glidescope, dexmedetomidine, coagulation analysis and TEE could facilitate anesthetic management in these patients.

  10. Anestesia venosa total em paciente portador de Osteogênesis imperfecta: relato de caso Anestesia venosa total en paciente portador de Osteogénesis imperfecta: relato de caso Total intravenous anesthesia in Osteogenesis imperfecta patient: case report

    Directory of Open Access Journals (Sweden)

    José Francisco Nunes Pereira das Neves

    2004-10-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A Osteogênesis Imperfecta é uma doença genética rara do tecido conjuntivo, com prevalência de 1/10000, que primariamente envolve a ossificação endocondral, resultando em ossos frágeis, múltiplas fraturas e deformidades esqueléticas. O objetivo desse artigo foi relatar um caso de paciente portador de Osteogenesis Imperfecta, submetido à anestesia venosa total para tratamento cirúrgico de fratura de fêmur. RELATO DO CASO: Paciente do sexo masculino, 15 anos, 41 kg, 140 cm, com história de Osteogênesis Imperfecta e cardiopatia, programado para tratamento cirúrgico de fratura do fêmur. Na sala de operação foi monitorizado com ECG, FC, PANI e SpO2 e submetido à anestesia geral venosa total com propofol, alfentanil e cisatracúrio. Após IOT, foi acrescentada monitorização da P ET CO2 e da temperatura esofágica. No período intra-operatório e na sala de recuperação pós-anestésica não apresentou complicações. Teve alta hospitalar no 5º dia de pós-operatório. CONCLUSÕES: O presente relato mostrou boa evolução intra e pós-operatória de paciente com Osteogênesis Imperfecta submetido à anestesia geral venosa total. A complexidade da doença mostrou a necessidade de avaliação e monitorização adequada pelo anestesiologista.JUSTIFICATIVA Y OBJETIVOS: La Osteogénesis Imperfecta es una rara enfermedad genética del tejido conjuntivo, con prevalencia de 1/10000, que primariamente envuelve la osificación endocondral, resultando en huesos frágiles, múltiplas fracturas e deformidades esqueléticas. El objetivo de ese artículo fue relatar un caso de paciente portador de Osteogénesis Imperfecta, sometido a anestesia venosa total para tratamiento quirúrgico de fractura de fémur. RELATO DEL CASO: Paciente del sexo masculino, 15 años, 41 kg, 140 cm, con historia de Osteogénesis Imperfecta y cardiopatía, programado para tratamiento quirúrgico de fractura del fémur. En la sala de operaci

  11. Effect of paternal age in achondroplasia, thanatophoric dysplasia, and osteogenesis imperfecta

    Energy Technology Data Exchange (ETDEWEB)

    Orioli, I.M. [Universidade Federal do Rio de Janeiro (Brazil); Castilla, E.E. [Centro de Educacion Medica e Investigacion Clinica, Buenos Aires (Argentina); Scarano, G.; Mastroiacovo, P. [Universita Cattolica, Rome (Italy)

    1995-11-06

    The paternal ages of nonfamilial cases of achondroplasia (AC) (n = 78), thanatophoric dysplasia (TD) (n = 64), and osteogenesis imperfecta (OI) (n = 106), were compared with those of matched controls, from an Italian Indagine Policentrica Italiana sulle Malformazioni Congenite (IPIMC) and a South American Estudio Colaborativo Latinoamericano de Malformaciones Congenitas (ECLAMC) series. The degree of paternal age effect on the origin of these dominant mutations differed among the three conditions. Mean paternal age was highly elevated in AC, 36.30 {plus_minus} 6.74 years in the IPIMC, and 37.19 {plus_minus} 10.53 years in the ECLAMC; less consistently elevated in TD, 33.60 {plus_minus} 7.08 years in the IPIMC, and 36.41 {plus_minus} 9.38 years in the ECLAMC; and only slightly elevated in OI in the ECLAMC, 31.15 {plus_minus} 9.25 years, but not in the IPIMC, 32.26 {plus_minus} 6.07 years. Increased maternal age or birth order in these conditions disappeared when corrected for paternal age. Approximately 50% of AC and TD cases, and only 30% of OI cases, were born to fathers above age 35 years. For AC and TD, the increase in relative incidence with paternal age fitted an exponential curve. The variability of paternal age effect in these new mutations could be due, among other reasons, to the high proportion of germ-line mosaicism in OI parents, or to the localization of the AC gene, mapped to the 4p16.3 region, in the neighborhood of an unstable DNA area. 28 refs., 1 fig., 6 tabs.

  12. Effect of sclerostin antibody treatment in a mouse model of severe osteogenesis imperfecta.

    Science.gov (United States)

    Roschger, Andreas; Roschger, Paul; Keplingter, Petra; Klaushofer, Klaus; Abdullah, Sami; Kneissel, Michaela; Rauch, Frank

    2014-09-01

    Osteogenesis imperfecta (OI) is a heritable bone fragility disorder that is usually caused by mutations affecting collagen type I production in osteoblasts. Stimulation of bone formation through sclerostin antibody treatment (Sost-ab) has shown promising results in mouse models of relatively mild OI. We assessed the effect of once-weekly intravenous Sost-ab injections for 4weeks in male Col1a1(Jrt)/+mice, a model of severe dominant OI, starting either at 4weeks (growing mice) or at 20weeks (adult mice) of age. Sost-ab had no effect on weight or femur length. In OI mice, no significant treatment-associated differences in serum markers of bone formation (alkaline phosphatase activity, procollagen type I N-propeptide) or resorption (C-telopeptide of collagen type I) were found. Micro-CT analyses at the femur showed that Sost-ab treatment was associated with higher trabecular bone volume and higher cortical thickness in wild type mice at both ages and in growing OI mice, but not in adult OI mice. Three-point bending tests of the femur showed that in wild type but not in OI mice, Sost-ab was associated with higher ultimate load and work to failure. Quantitative backscattered electron imaging of the femur did not show any effect of Sost-ab on CaPeak (the most frequently occurring calcium concentration in the bone mineral density distribution), regardless of genotype, age or measurement location. Thus, Sost-ab had a larger effect in wild type than in Col1a1(Jrt)/+mice. Previous studies had found marked improvements of Sost-ab on bone mass and strength in an OI mouse model with a milder phenotype. Our data therefore suggest that Sost-ab is less effective in a more severely affected OI mouse model.

  13. Targeting the LRP5 pathway improves bone properties in a mouse model of osteogenesis imperfecta.

    Science.gov (United States)

    Jacobsen, Christina M; Barber, Lauren A; Ayturk, Ugur M; Roberts, Heather J; Deal, Lauren E; Schwartz, Marissa A; Weis, MaryAnn; Eyre, David; Zurakowski, David; Robling, Alexander G; Warman, Matthew L

    2014-10-01

    The cell surface receptor low-density lipoprotein receptor-related protein 5 (LRP5) is a key regulator of bone mass and bone strength. Heterozygous missense mutations in LRP5 cause autosomal dominant high bone mass (HBM) in humans by reducing binding to LRP5 by endogenous inhibitors, such as sclerostin (SOST). Mice heterozygous for a knockin allele (Lrp5(p.A214V) ) that is orthologous to a human HBM-causing mutation have increased bone mass and strength. Osteogenesis imperfecta (OI) is a skeletal fragility disorder predominantly caused by mutations that affect type I collagen. We tested whether the LRP5 pathway can be used to improve bone properties in animal models of OI. First, we mated Lrp5(+/p.A214V) mice to Col1a2(+/p.G610C) mice, which model human type IV OI. We found that Col1a2(+/p.G610C) ;Lrp5(+/p.A214V) offspring had significantly increased bone mass and strength compared to Col1a2(+/p.G610C) ;Lrp5(+/+) littermates. The improved bone properties were not a result of altered mRNA expression of type I collagen or its chaperones, nor were they due to changes in mutant type I collagen secretion. Second, we treated Col1a2(+/p.G610C) mice with a monoclonal antibody that inhibits sclerostin activity (Scl-Ab). We found that antibody-treated mice had significantly increased bone mass and strength compared to vehicle-treated littermates. These findings indicate increasing bone formation, even without altering bone collagen composition, may benefit patients with OI.

  14. Copy number variants in association with type 1 collagenopathy: Atypical osteogenesis imperfecta.

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    Balasubramanian, Meena; Cartwright, Ashley; Smith, Kath; Arundel, Paul; Bishop, Nicholas J

    2016-02-01

    We report a sibling-pair and a 4-year old child from two families with an atypical presentation in Osteogenesis imperfecta (OI). In the sib-pair, the older sibling initially came to medical attention due to a fracture history (Patient 1) and she was shown to have a COL1A2 mutation. In addition, she also had developmental delay, facial dysmorphism, and a history of frequent infections which led to a search for an alternate diagnosis. ArrayCGH revealed a 4.3 Mb duplication on chromosome 19q13.42q13.43, which was confirmed by FISH analysis. On further familial analysis, the younger sibling who had no previous fracture history was also found to have the COL1A2 mutation and tested positive for the 19q13.42q13.43 duplication (Patient 2). The 19q13 duplication appears to be the cause of intellectual disability in these siblings but given that this is a chromosomal duplication, it is still possible that there is an as yet unidentified cause that may account for the combined phenotype in this family. Patient 3 was a 4-year old child presenting with a femoral fracture, blue sclerae, developmental delay, and joint hypermobility. Genetic analyses confirmed a COL1A2 mutation but also revealed an 8.8 Mb deletion of 11q24.2q25, confirmed by G-band chromosome analysis. We discuss the differing phenotypes in patients presenting with atypical OI and stress the need to consider ancillary investigations in individuals presenting with heterogeneous phenotypic symptoms, not entirely attributable to OI.

  15. Tracing the pathway between mutation and phenotype in osteogenesis imperfecta: Isolation of mineralization-specific genes

    Energy Technology Data Exchange (ETDEWEB)

    Culbert, A.A.; Wallis, G.A.; Kadler, K.E. [Univ. of Manchester (United Kingdom)

    1996-05-03

    The brittleness of bone in people with lethal (type II) osteogenesis imperfecta, a heritable disorder caused by mutations in the type I collagen genes, arises from the deposition of abnormal collagen in the bone matrix. The inability of the abnormal collagen to participate in mineralization may be caused by its failure to interact with other bone proteins. Here, we have designed a strategy to isolate the genes important for mineralization of collagen during bone formation. Cells isolated from 16-day embryonic chick calvaria and seeded post-confluence in culture deposited a mineralized matrix over a period of 2 weeks. Chick skin fibroblasts seeded and cultured under the same conditions did not mineralize. Using RT-PCR, we prepared short cDNAs ({approximately}300 bp) corresponding to the 3{prime} ends of mRNA from fibroblasts and separately from the mineralizing calvarial cells. Subtractive cDNA hybridization generated a pool of cDNAs that were specific to mineralizing calvarial cells but not to fibroblasts. Screening of 100,000 plaques of a chick bone ZAP Express cDNA library with this pool of mineralizing-specific cDNAs identified ten clones which comprised full-length cDNAs for the bone proteins osteopontin (eight of the ten positives), bone sialoprotein II (one of the ten positives), and cystatin (one of the ten positives). cDNAs for type I collagen, fibronectin, alkaline phosphatase, house-keeping genes, and other genes expressed in fibroblasts were not identified in this preliminary screen. The pool of short cDNAs is likely to comprise cDNAs for further bone-specific genes and will be used to screen the entire bone cDNA library of 4.2 million clones. 30 refs., 4 figs.

  16. Evaluation of a Modified Pamidronate Protocol for the Treatment of Osteogenesis Imperfecta.

    Science.gov (United States)

    Palomo, Telma; Andrade, Maria C; Peters, Barbara S E; Reis, Fernanda A; Carvalhaes, João Tomás A; Glorieux, Francis H; Rauch, Frank; Lazaretti-Castro, Marise

    2016-01-01

    Intravenous pamidronate is widely used to treat children with osteogenesis imperfecta (OI). In a well-studied protocol ('standard protocol'), pamidronate is given at a daily dose of 1 mg per kg body weight over 4 h on 3 successive days; infusion cycles are repeated every 4 months. Here, we evaluated renal safety of a simpler protocol for intravenous pamidronate infusions (2 mg per kg body weight given in a single infusion over 2 h, repeated every 4 months; 'modified protocol'). Results of 18 patients with OI types I, III, or IV treated with the modified protocol for 12 months were compared to 18 historic controls, treated with standard protocol. In the modified protocol, mild transient post-infusion increases in serum creatinine were found during each infusion but after 12 months serum creatinine remained similar from baseline [0.40 mg/dl (SD: 0.13)] to the end of the study [0.41 mg/dl (SD: 0.11)] (P = 0.79). The two protocols led to similar changes in serum creatinine during the first pamidronate infusion [modified protocol: +2% (SD: 21%); standard protocol: -3% (SD: 8%); P = 0.32]. Areal lumbar spine bone mineral density Z-scores increased from -2.7 (SD: 1.5) to -1.8 (SD: 1.4) with the modified protocol, and from -4.1 (SD: 1.4) to -3.1 (SD: 1.1) with standard protocol (P = 0.68 for group differences in bone density Z-score changes). The modified pamidronate protocol is safe and may have similar effects on bone density as the standard pamidronate protocol. More studies are needed with longer follow-up to prove anti-fracture efficacy.

  17. Femoral non-elongating rodding in osteogenesis imperfecta - The importance of purchasing epiphyseal plate

    Directory of Open Access Journals (Sweden)

    Wei-Chun Li

    2015-04-01

    Full Text Available Background: Corrective osteotomy and intramedullary rodding are widely used in children with osteogenesis imperfecta (OI, but revision rodding is often required. This study aims to investigate the effect of purchasing distal femoral epiphysis on the longevity of fixation using non-elongating rod. Methods: We investigated children with Sillence type III or IV OI who received antegrade femoral Rush rod fixations at age between 4 and 10 years in our institution. The fixations were classified into group A in which the rod reached distal femoral epiphysis and group B in which the rod stopped at femoral metaphysis. Failure of fixation is defined as rod cutting out of the cortex or when revision surgery was performed. Calculation of longevity of each rod fixation and Kaplan-Meier survival analysis were performed and compared between the two groups. Results: Eighteen children had the first femoral rodding at a mean age of 6.9 years and received a total of 61 femoral roddings with a mean follow-up of 11.4 years. Group A included 38 roddings performed at a mean age of 7.1 years and group B included 23 roddings performed at a mean age of 6.6 years. Group A had less revision rate (58% vs. 87%, more chance of survival > 3 years (74% vs. 43%, and longer median survival time (80 months vs. 33 months than group B. Conclusions: Less revision rate and better 3-year and 5-year survival rate were proved in the roddings that purchased epiphysis. We emphasize on using the precise implant length to purchase distal femoral epiphysis when non-elongating rod is the only available implant for fixation in children with OI.

  18. Echocardiographic Evidence of Early Diastolic Dysfunction in Asymptomatic Children with Osteogenesis Imperfecta

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    Khalfan S. Al-Senaidi

    2015-11-01

    Full Text Available Objectives: Structural and functional cardiovascular abnormalities have been reported in adults with osteogenesis imperfecta (OI; however, there is a lack of paediatric literature on this topic. This study aimed to investigate cardiovascular abnormalities in children with OI in comparison to a control group. Methods: This case-control study was conducted at the Sultan Qaboos University Hospital in Muscat, Oman, between May 2013 and August 2014. Data from eight patients with OI and 24 healthy controls were compared using conventional and tissue Doppler echocardiography (TDE. Results: The OI group had significantly lower peak early mitral valve flow velocity (P = 0.027, peak a-wave reversal in the pulmonary vein (P = 0.030 and peak early diastolic velocity of the mitral valve and upper septum (P = 0.001 each. The peak late diastolic velocities of the mitral valve (P = 0.002 and the upper septum (P = 0.037 were significantly higher in the OI group; however, the peak early/late diastolic velocity ratios of the mitral valve (P = 0.002 and upper septum (P = 0.001 were significantly lower. Left ventricular dimensions and aortic and pulmonary artery diameters were larger in the OI group when indexed for body surface area. Both groups had normal systolic cardiac function. Conclusion: Children with OI had normal systolic cardiac function. However, changes in myocardial tissue Doppler velocities were suggestive of early diastolic cardiac dysfunction. They also had increased left ventricular dimensions and greater vessel diameters. These findings indicate the need for early and detailed structural and functional echocardiographic assessment and follow-up of young patients with OI.

  19. Unique micro- and nano-scale mineralization pattern of human osteogenesis imperfecta type VI bone.

    Science.gov (United States)

    Fratzl-Zelman, Nadja; Schmidt, Ingo; Roschger, Paul; Roschger, Andreas; Glorieux, Francis H; Klaushofer, Klaus; Wagermaier, Wolfgang; Rauch, Frank; Fratzl, Peter

    2015-04-01

    Osteogenesis imperfecta (OI) is a heterogeneous group of inheritable connective tissue disorders characterized by mutation in genes involved in collagen synthesis and leading to increased bone fragility, low bone mass, impaired bone material properties and abnormally high bone matrix mineralization. Recessive OI type VI is caused by mutation in SERPINF1 leading to a loss-of-function of pigment epithelium-derived factor (PEDF) a collagen-binding protein with potent antiangiogenic activity. Affected patients develop a severe OI phenotype with a striking histological characteristic, rare in other OI types, of an excess of osteoid tissue and prolonged mineralization lag time. To get insights into matrix mineralization, we evaluated biopsies from 9 affected children by quantitative and by high-resolution backscattered electron imaging and assessed bone mineralization density distribution. Thickness, shape and arrangement of mineral particles were measured in a subset of 4 patients by synchrotron small angle X-ray scattering. Typical calcium content in the bone matrix was found to be increased compared to controls, even exceeding values found previously in OI patients with collagen-gene mutations. A main characteristic however, is the coexistence of this highly mineralized bone matrix with seams showing abnormally low mineral content. Atypical collagen fibril organization was found in the perilacunar region of young osteocytes, suggesting a disturbance in the early steps of mineralization. These observations are consistent with the presence of a heterogeneous population of mineral particles with unusual size, shape and arrangement, especially in the region with lower mineral content. The majority of the particles in the highly mineralized bone areas were less disorganized, but smaller and more densely packed than in controls and in previously measured OI patients. These data suggest that the lack of PEDF impairs a proper osteoblast-osteocyte transition and consequently

  20. Effect of paternal age in achondroplasia, thanatophoric dysplasia, and osteogenesis imperfecta.

    Science.gov (United States)

    Orioli, I M; Castilla, E E; Scarano, G; Mastroiacovo, P

    1995-11-01

    The paternal ages of nonfamilial cases of achondroplasia (AC) (n = 78), thanatophoric dysplasia (TD) (n = 64), and osteogenesis imperfecta (OI) (n = 106), were compared with those of matched controls, from an Italian Indagine Policentrica Italiana sulle Malformazioni Congenite and a South American Estudio Colaborativo Latinoamericano de Malformaciones Congénitas series. The degree of paternal age effect on the origin of these dominant mutations differed among the three conditions. Mean paternal age was highly elevated in AC, 36.30 +/- 6.74 years in the IPIMC, and 37.19 +/- 10.53 years in the ECLAMC; less consistently elevated in TD, 33.60 +/- 7.08 years in the IPIMC, and 36.41 +/- 9.38 years in the ECLAMC; and only slightly elevated in OI in the ECLAMC, 31.15 +/- 9.25 years, but not in the IPIMC, 32.26 +/- 6.07 years. Increased maternal age or birth order in these conditions disappeared when corrected for paternal age. Approximately 50% of AC and TD cases, and only 30% of OI cases, were born to fathers above age 35 years. For AC and TD, the increase in relative incidence with paternal age fitted an exponential curve. The variability of paternal age effect in these new mutations could be due, among other reasons, to the high proportion of germ-line mosaicism in OI parents, or to the localization of the AC gene, mapped to the 4p16.3 region, in the neighborhood of an unstable DNA area.

  1. Osteogenesis imperfecta - iconographic study of two cases and review of the literature; Osteogenese imperfeita - revisao da literatura e iconografia baseada em dois casos

    Energy Technology Data Exchange (ETDEWEB)

    Souza, Ricardo Pires de; Fernandes, Cintia; Hilario, Marcelo Cobra; Barros, Wagner Moraes; Soares, Aldemir Humberto [Hospital Heliopolis, Sao Paulo, SP (Brazil)

    1996-07-01

    The authors present a literature review about osteogenesis imperfecta, a disease that leads to bone fragility and low height patterns caused by an abnormality of the collagen synthesis. The iconographic study is based on two cases of the tarda type. (author) 9 refs., 3 figs.

  2. Pregnancy complicated by a severe form of foetal osteogenesis imperfecta in a 17-year-old primigravida: case report and overview of literature.

    Science.gov (United States)

    Madu, Anthony Emeka; Olamijulo, Joseph Ayodeji

    2013-05-01

    Abstract Osteogenesis imperfecta (OI) is an important inheritable thanetrophic disorder with wide ranging variable implications and prognosis for babies in utero and those who survive the perinatal period. The diagnosis of the severe forms can be readily made but some forms of the disease are known to go unrecognised until childhood.

  3. Mutations in FKBP10, which result in Bruck syndrome and recessive forms of osteogenesis imperfecta, inhibit the hydroxylation of telopeptide lysines in bone collagen

    NARCIS (Netherlands)

    Schwarze, Ulrike; Cundy, Tim; Pyott, Shawna M.; Christiansen, Helena E.; Hegde, Madhuri R.; Bank, Ruud A.; Pals, Gerard; Ankala, Arunkanth; Conneely, Karen; Seaver, Laurie; Yandow, Suzanne M.; Raney, Ellen; Babovic-Vuksanovic, Dusica; Stoler, Joan; Ben-Neriah, Ziva; Segel, Reeval; Lieberman, Sari; Siderius, Liesbeth; Al-Aqeel, Aida; Hannibal, Mark; Hudgins, Louanne; McPherson, Elizabeth; Clemens, Michele; Sussman, Michael D.; Steiner, Robert D.; Mahan, John; Smith, Rosemarie; Anyane-Yeboa, Kwame; Wynn, Julia; Chong, Karen; Uster, Tami; Aftimos, Salim; Sutton, V. Reid; Davis, Elaine C.; Kim, Lammy S.; Weis, Mary Ann; Eyre, David; Byers, Peter H.

    2013-01-01

    Although biallelic mutations in non-collagen genes account for 10 of individuals with osteogenesis imperfecta, the characterization of these genes has identified new pathways and potential interventions that could benefit even those with mutations in type I collagen genes. We identified mutations in

  4. A novel homozygous variant in SERPINH1 associated with a severe, lethal presentation of osteogenesis imperfecta with hydranencephaly.

    Science.gov (United States)

    Marshall, Charlotte; Lopez, Jaime; Crookes, Laura; Pollitt, Rebecca C; Balasubramanian, Meena

    2016-12-20

    Osteogenesis imperfecta (OI) is a genetic disorder characterised by low bone mineral density resulting in fractures. 85-90% of patients with OI carry a variant in the type 1 collagen genes, COL1A1 and COL1A2, which follows an autosomal dominant pattern of inheritance. However, within the last two decades, there have been growing number of variants identified in genes that follow an autosomal recessive pattern of inheritance. Our proband is a child born in Mexico with multiple fractures of ribs, minimal calvarial mineralisation, platyspondyly, marked compression and deformed long bones. He also presented with significant hydranencephaly, requiring ventilatory support from birth, and died at 8days of age. A homozygous c.338_357delins22 variant in exon 2 of SERPINH1 was identified. This gene encodes heat shock protein 47, a collagen-specific chaperone which binds to the procollagen triple helix and is responsible for collagen stabilisation in the endoplasmic reticulum. There is minimal literature on the mechanism of action for variants in SERPINH1 resulting in osteogenesis imperfecta. Here we discuss this rare, previously unreported variant, and expand on the phenotypic presentation of this novel variant resulting in a severe, lethal phenotype of OI in association with hydranencephaly.

  5. Molecular Mechanism of Osteogenesis Imperfecta%成骨不全的分子机制

    Institute of Scientific and Technical Information of China (English)

    徐超; 韩金祥; 鲁艳芹

    2012-01-01

    成骨不全是一类临床表现为骨质脆弱、易骨折等特征的罕见遗传性疾病.绝大多数(90%以上)显性患者发病系由Ⅰ型前胶原α链COLlA1和COLl A2基因突变引起胶原合成量不足,或结构改变.少数隐性患者发病为其他相关基因突变导致胶原翻译后过度修饰、折叠、装配和分泌过程异常.本文就成骨不全发病的遗传学及分子生物学机制作一综述.%Osteogenesis imperfecta ( OI) is a kind of rare genetic disease characterized by increased bone fragility and easy to fracture. Clinical symptoms include frequent bone fracture, short stature, blue sclera, dentinogenesis imperfecta and hearing loss. OI is a heterogeneous disease; its patterns of inheritance are predominated by autosomal dominant, but the autosomal recessive inheritance is rare. Patterns of clinical phenotype vary from mild to perinatal lethal one. Based on traditional silence type system of I-IV, type V-XII has been described till now. Ten different genes have been reported to cause OI. The genetic cause for type V is still unknown. COLlAl and C0LIA2, which encode the a chains of type I procollagen, are the main OI-related genes and relate to autosomal dominant OI. Mutations in these two genes lead to 90% of OI cases. The vast majority mutations of COLlAl and C0L1A2 are Gly substitution. In addition, eight different gene defect associated with recessive genetic OI have been reported in recent years. CRTAP, LEPREX and PPIB encode CRTAP, P3H1 and CyPB, respectively. They assemble into 3-hydroxylation complex which participates in posttranslational modification of collagen I. As chaperones, FKBP65 encoded by FKBP10 and HSP47 encoded by SERPINHl take part in the process of folding and assembling of collagen type I. OSX is a kind of transcription factor, which might be expected to play an important role in osteoblast differentiation. SERPINFl is close contact with metabolic disorder of bone. BMP1 defect is reported to cause

  6. First mouse model for combined osteogenesis imperfecta and Ehlers-Danlos syndrome.

    Science.gov (United States)

    Chen, Frieda; Guo, Ruolin; Itoh, Shousaku; Moreno, Luisa; Rosenthal, Esther; Zappitelli, Tanya; Zirngibl, Ralph A; Flenniken, Ann; Cole, William; Grynpas, Marc; Osborne, Lucy R; Vogel, Wolfgang; Adamson, Lee; Rossant, Janet; Aubin, Jane E

    2014-06-01

    By using a genome-wide N-ethyl-N-nitrosourea (ENU)-induced dominant mutagenesis screen in mice, a founder with low bone mineral density (BMD) was identified. Mapping and sequencing revealed a T to C transition in a splice donor of the collagen alpha1 type I (Col1a1) gene, resulting in the skipping of exon 9 and a predicted 18-amino acid deletion within the N-terminal region of the triple helical domain of Col1a1. Col1a1(Jrt) /+ mice were smaller in size, had lower BMD associated with decreased bone volume/tissue volume (BV/TV) and reduced trabecular number, and furthermore exhibited mechanically weak, brittle, fracture-prone bones, a hallmark of osteogenesis imperfecta (OI). Several markers of osteoblast differentiation were upregulated in mutant bone, and histomorphometry showed that the proportion of trabecular bone surfaces covered by activated osteoblasts (Ob.S/BS and N.Ob/BS) was elevated, but bone surfaces undergoing resorption (Oc.S/BS and N.Oc/BS) were not. The number of bone marrow stromal osteoprogenitors (CFU-ALP) was unaffected, but mineralization was decreased in cultures from young Col1a1(Jrt) /+ versus +/+ mice. Total collagen and type I collagen content of matrices deposited by Col1a1(Jrt) /+ dermal fibroblasts in culture was ∼40% and 30%, respectively, that of +/+ cells, suggesting that mutant collagen chains exerted a dominant negative effect on type I collagen biosynthesis. Mutant collagen fibrils were also markedly smaller in diameter than +/+ fibrils in bone, tendon, and extracellular matrices deposited by dermal fibroblasts in vitro. Col1a1(Jrt) /+ mice also exhibited traits associated with Ehlers-Danlos syndrome (EDS): Their skin had reduced tensile properties, tail tendon appeared more frayed, and a third of the young adult mice had noticeable curvature of the spine. Col1a1(Jrt) /+ is the first reported model of combined OI/EDS and will be useful for exploring aspects of OI and EDS pathophysiology and treatment.

  7. Ultrastructural and histological findings on examination of skin in osteogenesis imperfecta: a novel study.

    Science.gov (United States)

    Balasubramanian, Meena; Wagner, Bart E; Peres, Luiz C; Sobey, Glenda J; Parker, Michael J; Dalton, Ann; Arundel, Paul; Bishop, Nicholas J

    2015-04-01

    Osteogenesis imperfecta (OI) is a heterogeneous group of inherited disorders of bone formation, resulting in low bone mass and an increased propensity for fractures. It is a variable condition with a range of clinical severities. The histological and ultrastructural findings in the skin of patients with OI have not been described in detail in the previously published literature. Although protein analysis of cultured fibroblasts has historically been used in the diagnostic work-up of OI patients, other aspects of skin examination are not routinely performed as part of the diagnostic pathway in patients with OI. The aims of this study were to perform histological and ultrastructural examination of skin biopsies in patients with OI. This was to identify common and distinguishing features in the numerous genetically distinct subtypes of OI and compare the findings with those in patients who did not present with fractures, and to enable the use of the results thus obtained to aid in the diagnostic work-up of patients with OI. As part of a larger research study set-up to identify clinical features and natural history in patients with atypical features of OI, skin biopsy and examination (histology and electron microscopy) were undertaken. Genetic analysis and ancillary investigations were also performed to identify similarities within this group and to differentiate this group from the 'normal' population. At the end of this study, we were able to demonstrate that the histological and electron microscopic findings on a skin biopsy may be an indicator of the likelihood of identifying a pathogenic mutation in type 1 collagen genes. This is because patients with specific findings on examination, such as elastic fibre area fraction (on histological analysis), collagen fibril diameter variability, deviation from the expected mean and collagen flowers (on electron microscopy), are more likely to be positive on genetic analyses. This has, in turn, provided more insight into the

  8. Therapeutic impact of low amplitude high frequency whole body vibrations on the osteogenesis imperfecta mouse bone.

    Science.gov (United States)

    Vanleene, Maximilien; Shefelbine, Sandra J

    2013-04-01

    Osteogenesis imperfecta (OI) is characterized by extremely brittle bone. Currently, bisphosphonate drugs allow a decrease of fracture by inhibiting bone resorption and increasing bone mass but with possible long term side effects. Whole body mechanical vibrations (WBV) treatment may offer a promising route to stimulate bone formation in OI patients as it has exhibited health benefits on both muscle and bone mass in human and animal models. The present study has investigated the effects of WBV (45Hz, 0.3g, 15minutes/days, 5days/week) in young OI (oim) and wild type female mice from 3 to 8weeks of age. Vibration therapy resulted in a significant increase in the cortical bone area and cortical thickness in the femur and tibia diaphysis of both vibrated oim and wild type mice compared to sham controls. Trabecular bone was not affected by vibration in the wild type mice; vibrated oim mice, however, exhibited significantly higher trabecular bone volume fraction in the proximal tibia. Femoral stiffness and yield load in three point bending were greater in the vibrated wild type mice than in sham controls, most likely attributed to the increase in femur cortical cross sectional area observed in the μCT morphology analyses. The vibrated oim mice showed a trend toward improved mechanical properties, but bending data had large standard deviations and there was no significant difference between vibrated and non-vibrated oim mice. No significant difference of the bone apposition was observed in the tibial metaphyseal trabecular bone for both the oim and wild type vibrated mice by histomorphometry analyses of calcein labels. At the mid diaphysis, the cortical bone apposition was not significantly influenced by the WBV treatment in both the endosteum and periosteum of the oim vibrated mice while a significant change is observed in the endosteum of the vibrated wild type mice. As only a weak impact in bone apposition between the vibrated and sham groups is observed in the

  9. Benefit of infusions with ibandronate treatment in children with osteogenesis imperfecta

    Institute of Scientific and Technical Information of China (English)

    LI Mei; MENG Xun-wu; XU Ling; XIA Wei-bo; XING Xiao-ping; YU Wei; HU Ying-ying; JIANG Yan; WANG Ou; LIU Hai-juan; HAN Lan-wen

    2011-01-01

    Background Osteogenesis imperfecta (OI) is a rare bone disease and its effective treatment is relatively deficient. We tried to assess the effects of new bisphosphonate, ibandronate on children with OI.Methods In this open-label, prospective, controlled study, 30 children with OI were enrolled. They received either infusions of ibandronate (2 mg) in every three months or oral calcitriol 0.25 μg daily for 24 months. All patients took 500 mg calcium plus 200 U vitamin D daily together. The endpoints were the change of annual new fracture rate (observed by case history and X ray films of spine), bone mineral density (BMD, measured by dual energy X-ray absortiometry), serum concentration of carboxy-telopeptide cross-links of type Ⅰ collagen (CTX, bone resorption marker) and alkaline phosphatase (ALP, bone formation marker) during the follow-up.Results After the cyclic infusions of ibandronate, the annual new fracture rate was significantly decreased from 1.9 to 0.13 time, obviously lower than that of calcitriol group, which decreased from 1.8 to 1.0 time after the treatment (P <0.001).The significant increase of BMD at the lumbar spine, femoral neck, trochanter, total hip was found in the group of ibandronate by 59.0%, 42.0%, 47.5% and 36.6% in time dependent manner (compared with the baseline, P <0.001). The increase of BMD in ibandronate group was greater than that of calcitriol group (P <0.001). The concentrations of ALP and CTX were obviously decreased in ibandronate group, and the reduction of CTX was more significant than that of ALP (P <0.001). The tolerance of the children to ibandronate was quite well. Mild fever and muscle pain were found in 9 cases within 1-3 days after the first infusion of ibandronate, which could relieve after 1-2 days without special management.Conclusions The benefits of cyclic infusions of ibandronate to children with OI are significant because ibandronate could significantly reduce annual bone fracture rate

  10. Osteogenesis imperfecta combined with osteonecrosis of the femoral head:1 case report%成骨不全症合并股骨头坏死一例

    Institute of Scientific and Technical Information of China (English)

    吴李菲; 蔡贤华; 黄卫兵; 夏平光

    2014-01-01

    Osteogenesis imperfecta ( OI ) is a genetically and clinically heterogeneous disorder of the bone and connective tissues characterized by osteoporosis, fragile bones, hyperextensible joints, dentinogenesis imperfecta, bluish coloration of the sclerae, and adult-onset hearing loss. One case of young patient treated in our department was diagnosed with OI and osteonecrosis of the femoral head ( ONFH ) by medical history, family history and imagingdata. After the treatment of percutaneous decompression procedure, his imaging data and the Harris score of both hip joints conifrmed the surgery was effective.

  11. NOVEL SPLICING MUTATION OF COL1A1 GENE CAUSING OSTEOGENESIS IMPERFECTA TYPE I IN CHINESE PEDIGREE

    Institute of Scientific and Technical Information of China (English)

    WU Xiao-lin; GU Ming-min; CUI Bing; LI Xi-hua; LU Zhen-yu; WANG Zhu-gang; YUAN Wen-tao; SONG Huai-dong

    2007-01-01

    Objective To detect the peculiar mutation in a Chinese family with osteogenesis imperfecta,COL1A1 and COL1A2 being analysed. Methods A genome screen was undertaken covering COL1A1 at 17q21-22 and COL1A2 at 7q22.1. The Linkage ( Version 5.1 ) was used for 2-point analysis. DNA sequencing was used to screen and identify the mutation. Results A linkage to the markers on chromosome 17q21-22 was observed. Sequence analysis of COL1A1 revealed a splicing mutation ( IVS8-2A > G) that converted the 3' end of intron 8 from AG to GG. Conclusion This mutation ( IVS 8-2A > G) is novel, and has not yet been registered in the Human Type Ⅰ and Type Ⅲ Collagen Mutations Database.

  12. Microstructure and compressive mechanical properties of cortical bone in children with osteogenesis imperfecta treated with bisphosphonates compared with healthy children.

    Science.gov (United States)

    Imbert, Laurianne; Aurégan, Jean-Charles; Pernelle, Kélig; Hoc, Thierry

    2015-06-01

    Osteogenesis imperfecta (OI) is a genetic disorder characterized by a change in bone tissue quality, but little data are available to describe the factors involved at the macroscopic scale. To better understand the effect of microstructure alterations on the mechanical properties at the sample scale, we studied the structural and mechanical properties of six cortical bone samples from children with OI treated with bisphosphonates and compared them to the properties of three controls. Scanning electron microscopy, high resolution computed tomography and compression testing were used to assess these properties. More resorption cavities and a higher osteocyte lacunar density were observed in OI bone compared with controls. Moreover, a higher porosity was measured for OI bones along with lower macroscopic Young's modulus, yield stress and ultimate stress. The microstructure was impaired in OI bones; the higher porosity and osteocyte lacunar density negatively impacted the mechanical properties and made the bone more prone to fracture.

  13. Hyperplastic callus formation in osteogenesis imperfecta type V: follow-up of three generations over ten years

    Energy Technology Data Exchange (ETDEWEB)

    Cheung, Moira S.; Azouz, E.M.; Glorieux, Francis H. [Shriners Hospital for Children and McGill University, Genetics Unit, Montreal, Quebec (Canada); Rauch, Frank [Shriners Hospital for Children and McGill University, Genetics Unit, Montreal, Quebec (Canada); Shriners Hospital for Children, Genetics Unit, Montreal, Quebec (Canada)

    2008-05-15

    Hyperplastic callus (HPC) formation is a prominent feature of osteogenesis imperfecta (OI) type V; however, little is known about its long-term outcome. In this case report we describe the occurrence, appearance and course of a femoral HPC in a patient with OI type V during 10 years of follow-up. Radiographs of HPC in this child were compared and contrasted with HPC formation in the femur of his father and paternal grandfather, who also were affected with OI type V. This case report makes it clear that HPC can lead to significant morbidity, not only in the acute phase but also long term as a result of residual alteration in bone architecture. (orig.)

  14. Advances in the research of osteogenesis imperfecta%成骨不全的相关研究进展

    Institute of Scientific and Technical Information of China (English)

    周琦; 白露

    2014-01-01

    成骨不全(osteogenesis imperfecta,OI)又称为脆骨症,是一种以骨受累为主要特征的先天性全身性结缔组织遗传疾病.该病致病机理复杂,遗传异质性高,其中90%的OI是由Ⅰ型胶原基因(COL1A1,COL1A2)突变导致结构或功能的异常引起的.目前治疗OI主要是使用药物或进行外科手术,但基因治疗将成为治疗该病的根本途径和主要研究热点.

  15. Severe osteogenesis imperfecta Type-III and its challenging treatment in newborn and preschool children. A systematic review.

    Science.gov (United States)

    Sinikumpu, Juha-Jaakko; Ojaniemi, Marja; Lehenkari, Petri; Serlo, Willy

    2015-08-01

    Osteogenesis imperfecta (OI) is a group of genetic disorders, of which Type III is the most severe among survivors. The disease is characterised in particular by bone fragility, decreased bone mass and increased incidence of fractures. Other usual findings are muscle hypotonia, joint hypermobility and short stature. Fractures and weak bones may consequently cause limb and spinal deformity and chronic physical disability. Bisphosphonates have revolutionised the treatment of newborn children with severe OI type III. Surgery is still needed in most patients due to high frequency of the fractures. In this systematic review we describe the present state-of-art in treating the most severe type of OI in newborn and preschool children with their bone fractures.

  16. Rib cage deformities alter respiratory muscle action and chest wall function in patients with severe osteogenesis imperfecta.

    Directory of Open Access Journals (Sweden)

    Antonella LoMauro

    Full Text Available BACKGROUND: Osteogenesis imperfecta (OI is an inherited connective tissue disorder characterized by bone fragility, multiple fractures and significant chest wall deformities. Cardiopulmonary insufficiency is the leading cause of death in these patients. METHODS: Seven patients with severe OI type III, 15 with moderate OI type IV and 26 healthy subjects were studied. In addition to standard spirometry, rib cage geometry, breathing pattern and regional chest wall volume changes at rest in seated and supine position were assessed by opto-electronic plethysmography to investigate if structural modifications of the rib cage in OI have consequences on ventilatory pattern. One-way or two-way analysis of variance was performed to compare the results between the three groups and the two postures. RESULTS: Both OI type III and IV patients showed reduced FVC and FEV(1 compared to predicted values, on condition that updated reference equations are considered. In both positions, ventilation was lower in OI patients than control because of lower tidal volume (p<0.01. In contrast to OI type IV patients, whose chest wall geometry and function was normal, OI type III patients were characterized by reduced (p<0.01 angle at the sternum (pectus carinatum, paradoxical inspiratory inward motion of the pulmonary rib cage, significant thoraco-abdominal asynchronies and rib cage distortions in supine position (p<0.001. CONCLUSIONS: In conclusion, the restrictive respiratory pattern of Osteogenesis Imperfecta is closely related to the severity of the disease and to the sternal deformities. Pectus carinatum characterizes OI type III patients and alters respiratory muscles coordination, leading to chest wall and rib cage distortions and an inefficient ventilator pattern. OI type IV is characterized by lower alterations in the respiratory function. These findings suggest that functional assessment and treatment of OI should be differentiated in these two forms of the

  17. A cross-sectional multicenter study of osteogenesis imperfecta in North America - results from the linked clinical research centers.

    Science.gov (United States)

    Patel, R M; Nagamani, S C S; Cuthbertson, D; Campeau, P M; Krischer, J P; Shapiro, J R; Steiner, R D; Smith, P A; Bober, M B; Byers, P H; Pepin, M; Durigova, M; Glorieux, F H; Rauch, F; Lee, B H; Hart, T; Sutton, V R

    2015-02-01

    Osteogenesis imperfecta (OI) is the most common skeletal dysplasia that predisposes to recurrent fractures and bone deformities. In spite of significant advances in understanding the genetic basis of OI, there have been no large-scale natural history studies. To better understand the natural history and improve the care of patients, a network of Linked Clinical Research Centers (LCRC) was established. Subjects with OI were enrolled in a longitudinal study, and in this report, we present cross-sectional data on the largest cohort of OI subjects (n = 544). OI type III subjects had higher prevalence of dentinogenesis imperfecta, severe scoliosis, and long bone deformities as compared to those with OI types I and IV. Whereas the mean lumbar spine area bone mineral density (LS aBMD) was low across all OI subtypes, those with more severe forms had lower bone mass. Molecular testing may help predict the subtype in type I collagen-related OI. Analysis of such well-collected and unbiased data in OI can not only help answering questions that are relevant to patient care but also foster hypothesis-driven research, especially in the context of 'phenotypic expansion' driven by next-generation sequencing.

  18. Osteogenesis imperfecta Type VI with severe bony deformities caused by novel compound heterozygous mutations in SERPINF1.

    Science.gov (United States)

    Cho, Sung Yoon; Ki, Chang-Seok; Sohn, Young Bae; Kim, Su Jin; Maeng, Se Hyun; Jin, Dong-Kyu

    2013-07-01

    Osteogenesis imperfecta (OI) comprises a heterogeneous group of disorders characterized by bone fragility, frequent fractures, and low bone mass. Dominantly inherited COL1A1 or COL1A2 mutations appear to be causative in the majority of OI types, but rare recessively inherited genes have also been reported. Recently, SERPINF1 has been reported as another causative gene in OI type VI. To date, only eight SERPINF1 mutations have been reported and all are homozygous. Our patient showed no abnormalities at birth, frequent fractures, osteopenia, and poor response on pamidronate therapy. At the time of her most recent evaluation, she was 8 yr old, and could not walk independently due to frequent lower-extremity fractures, resulting in severe deformity. No clinical signs were seen of hearing impairment, blue sclera, or dentinogenesis imperfecta. In this study, we describe the clinical and radiological findings of one Korean patient with novel compound heterozygous mutations (c.77dupC and c.421dupC) of SERPINF1.

  19. Clinical Aspects, Imaging Features, and Considerations on Bisphosphonate-Related Osteonecrosis Risk in a Pediatric Patient with Osteogenesis Imperfecta

    Directory of Open Access Journals (Sweden)

    Fábio Wildson Gurgel Costa

    2014-01-01

    Full Text Available Osteogenesis imperfecta (OI is a rare hereditary condition caused by changes in collagen metabolism. It is classified into four types according to clinical, genetic, and radiological criteria. Clinically, bone fragility, short stature, blue sclerae, and locomotion difficulties may be observed in this disease. OI is often associated to severe dental problems, such as dentinogenesis imperfecta (DI and malocclusions. Radiographically, affected teeth may have crowns with bulbous appearance, accentuated constriction in the cementoenamel junction, narrowed roots, large root canals due to defective dentin formation, and taurodontism (enlarged pulp chambers. There is no definitive cure, but bisphosphonate therapy is reported to improve bone quality; however, there is a potential risk of bisphosphonate-related osteonecrosis of the jaw. In this study we report a case of OI in a male pediatric patient with no family history of OI who was receiving ongoing treatment with intravenous perfusion of bisphosphonate and who required dental surgery. In addition, we discussed the clinical and imaging findings and briefly reviewed the literature.

  20. Two novel distinct COL1A2 mutations highlight the complexity of genotype-phenotype correlations in osteogenesis imperfecta and related connective tissue disorders.

    Science.gov (United States)

    Reuter, Miriam S; Schwabe, Georg C; Ehlers, Christian; Marschall, Christoph; Reis, André; Thiel, Christian; Graul-Neumann, Luitgard

    2013-12-01

    Osteogenesis imperfecta is a heritable connective tissue disorder characterized by variable symptoms including predisposition to fractures. Despite the identification of numerous mutations, a reliable genotype-phenotype correlation has remained notoriously difficult. We now describe two patients with osteogenesis imperfecta and novel, so far undescribed mutations in the COL1A2 gene, further highlighting this complexity. A 3-year-old patient presented with features reminiscent of a connective tissue disorder, with joint hypermobility, Wormian bones, streaky lucencies in the long bones and relative macrocephaly. The patient carried a heterozygous c.1316G > A (p.Gly439Asp) mutation in the COL1A2 gene located in a triple-helix region, in which glycine substitutions have been assumed to cause perinatal lethal OI (Sillence type II). A second family with type I osteogenesis imperfecta carried a heterozygous nonsense mutation c.4060C > T (p.Gln1354X) within the last exon of COL1A2. Whereas other heterozygous nonsense mutations in COL1A2 do not lead to a phenotype, in this case the mRNA is presumed to escape nonsense-mediated decay. Therefore the predicted COL1A2 propeptide lacks the last 13 C-terminal amino acids, suggesting that the OI phenotype results from decelerated assembly and overmodification of the collagen triple helix. The presented COL1A2 mutations exemplify the complexity of COL1A2 genotype-phenotype correlation in genetic counselling in OI.

  1. Radiological manifestations of biphosphonate treatment with APD in a child suffering from osteogenesis imperfecta

    Energy Technology Data Exchange (ETDEWEB)

    Devogelaer, J.P.; Deuxchaisnes, C.N. de; Malghem, J.; Maldague, B.

    1987-07-01

    A 12-year-old female suffering fromosteogenesis imperfecta (OI) was treated with 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (APD) orally, 250 mg daily, for periods of 2 months, alternating with periods of 2 months of abstinence. Total duration of therapy was 1 year. Radiological and clinical improvement was striking. Furthermore, X-rays of the bones showed large, parallel radio-opaque striae, corresponding exactly to the periods of therapy. These were present in all metaphyses.

  2. Osteogenesis imperfecta model peptides: incorporation of residues replacing Gly within a triple helix achieved by renucleation and local flexibility.

    Science.gov (United States)

    Xiao, Jianxi; Madhan, Balaraman; Li, Yingjie; Brodsky, Barbara; Baum, Jean

    2011-07-20

    Missense mutations, which replace one Gly with a larger residue in the repeating sequence of the type I collagen triple helix, lead to the hereditary bone disorder osteogenesis imperfecta (OI). Previous studies suggest that these mutations may interfere with triple-helix folding. NMR was used to investigate triple-helix formation in a series of model peptides where the residue replacing Gly, as well as the local sequence environment, was varied. NMR measurement of translational diffusion coefficients allowed the identification of partially folded species. When Gly was replaced by Ala, the Ala residue was incorporated into a fully folded triple helix, whereas replacement of Gly by Ser or Arg resulted in the presence of some partially folded species, suggesting a folding barrier. Increasing the triple-helix stability of the sequence N-terminal to a Gly-to-Ser replacement allowed complete triple-helix folding, whereas with the substitution of Arg, with its large side chain, the peptide achieved full folding only after flexible residues were introduced N-terminal to the mutation site. These studies shed light on the factors important for accommodation of Gly mutations within the triple helix and may relate to the varying severity of OI.

  3. Administration of soluble activin receptor 2B increases bone and muscle mass in a mouse model of osteogenesis imperfecta

    Institute of Scientific and Technical Information of China (English)

    Douglas J DiGirolamo; Vandana Singhal; Xiaoli Chang; Se-Jin Lee; Emily L Germain-Lee

    2015-01-01

    Osteogenesis imperfecta (OI) comprises a group of heritable connective tissue disorders generally defined by recurrent fractures, low bone mass, short stature and skeletal fragility. Beyond the skeletal complications of OI, many patients also report intolerance to physical activity, fatigue and muscle weakness. Indeed, recent studies have demonstrated that skeletal muscle is also negatively affected by OI, both directly and indirectly. Given the well-established interdependence of bone and skeletal muscle in both physiology and pathophysiology and the observations of skeletal muscle pathology in patients with OI, we investigated the therapeutic potential of simultaneous anabolic targeting of both bone and skeletal muscle using a soluble activin receptor 2B (ACVR2B) in a mouse model of type III OI (oim). Treatment of 12-week-old oim mice with ACVR2B for 4 weeks resulted in significant increases in both bone and muscle that were similar to those observed in healthy, wild-type littermates. This proof of concept study provides encouraging evidence for a holistic approach to treating the deleterious consequences of OI in the musculoskeletal system.

  4. Transplanted bone marrow mononuclear cells and MSCs impart clinical benefit to children with osteogenesis imperfecta through different mechanisms.

    Science.gov (United States)

    Otsuru, Satoru; Gordon, Patricia L; Shimono, Kengo; Jethva, Reena; Marino, Roberta; Phillips, Charlotte L; Hofmann, Ted J; Veronesi, Elena; Dominici, Massimo; Iwamoto, Masahiro; Horwitz, Edwin M

    2012-08-30

    Transplantation of whole bone marrow (BMT) as well as ex vivo-expanded mesenchymal stromal cells (MSCs) leads to striking clinical benefits in children with osteogenesis imperfecta (OI); however, the underlying mechanism of these cell therapies has not been elucidated. Here, we show that non-(plastic)-adherent bone marrow cells (NABMCs) are more potent osteoprogenitors than MSCs in mice. Translating these findings to the clinic, a T cell-depleted marrow mononuclear cell boost (> 99.99% NABMC) given to children with OI who had previously undergone BMT resulted in marked growth acceleration in a subset of patients, unambiguously indicating the therapeutic potential of bone marrow cells for these patients. Then, in a murine model of OI, we demonstrated that as the donor NABMCs differentiate to osteoblasts, they contribute normal collagen to the bone matrix. In contrast, MSCs do not substantially engraft in bone, but secrete a soluble mediator that indirectly stimulates growth, data which provide the underlying mechanism of our prior clinical trial of MSC therapy for children with OI. Collectively, our data indicate that both NABMCs and MSCs constitute effective cell therapy for OI, but exert their clinical impact by different, complementary mechanisms. The study is registered at www.clinicaltrials.gov as NCT00187018.

  5. An unusual case of atrophic mandible fracture in a patient with osteogenesis imperfecta and on oral bisphosphonate therapy: Case report

    Directory of Open Access Journals (Sweden)

    Abdulrahman Al-Osaimi

    2014-04-01

    Full Text Available Fractures of severely atrophic (height < 10 mm edentulous mandibles are infrequent and challenging to manage. Factors such as sclerotic bone and decreased vascularity combined with systemic diseases complicate the management of such fractures. Osteogenesis imperfecta (OI is a heterogeneous group of inherited disorders of type I collagen metabolism. Patients with OI characteristically present with histories of long bone fractures, deformities, blue sclerae, and opalescent dentin. However, fractures of the facial skeleton are rare. Bisphosphonate therapy has been proven to effectively reduce the fracture risk in patients with OI. The purpose of this clinical report is to present an unusual case of spontaneous fracture of the atrophic mandible in a patient with OI. Despite open reduction and internal fixation (ORIF with miniplate osteosynthesis, the patient developed a second fracture at a screw placement site distal to the first fracture. The patient was successfully treated with ORIF using locking reconstruction plates fixed in the symphyseal and angle regions. Bone healing following ORIF was normal, and no clinical sign of osteonecrosis as a result of bisphosphonate therapy was observed. Patients with OI can present with spontaneous fractures of already weakened mandibles. Although such fractures can be managed with care using established protocols, further research is required to examine the effects of concomitant medication, such as bisphosphonates.

  6. Osteogenesis imperfecta type I: Molecular heterogeneity for COL1A1 null alleles of type I collagen

    Energy Technology Data Exchange (ETDEWEB)

    Willing, M.C.; Deschenes, S.P.; Pitts, S.H.; Arikat, H.; Roberts, E.J.; Scott, D.A.; Slayton, R.L. [Univ. of Iowa, Iowa City, IA (United States); Byers, P.H. [Univ. of Washington, Seattle, WA (United States)

    1994-10-01

    Osteogenesis imperfecta (OI) type I is the mildest form of inherited brittle-bone disease. Dermal fibroblasts from most affected individuals produce about half the usual amount of type I procollagen, as a result of a COL1A1 {open_quotes}null{close_quotes} allele. Using PCR amplification of genomic DNA from affected individuals, followed by denaturing gradient gel electrophoresis (DGGE) and SSCP, we identified seven different COL1A1 gene mutations in eight unrelated families with OI type I. Three families have single nucleotide substitutions that alter 5{prime} donor splice sites; two of these unrelated families have the same mutation. One family has a point mutation, in an exon, that creates a premature termination codon, and four have small deletions or insertions, within exons, that create translational frameshifts and new termination codons downstream of the mutation sites. Each mutation leads to both marked reduction in steady-state levels of mRNA from the mutant allele and a quantitative decrease in type I procollagen production. Our data demonstrate that different molecular mechanisms that have the same effect on type I collagen production result in the same clinical phenotype. 58 refs., 4 figs., 1 tab.

  7. Osteogenesis Imperfecta with Celiac Disease and Type II Diabetes Mellitus Associated: Improvement with a Gluten-Free Diet

    Directory of Open Access Journals (Sweden)

    Luis Rodrigo

    2012-01-01

    Full Text Available Osteogenesis imperfecta (OI is a genetic disease, with a connective tissue alteration, consisting in the presence of multiple spontaneous fractures or after minimal traumatism. Its association with other metabolic processes is rarely described. We present the clinical case of a female adult patient of 43 years. From her infancy, she has had multiple fractures, needing several surgical interventions, and she was diagnosed of OI type 2 at adolescence age. Due mainly to difficulties in walking remaining in wheel-chair in the last three years, she was overweight with morbid obesity (BMI=45.4 and had a type-II DM associated. She suffered from recurrent abdominal pain and chronic diarrhea and was diagnosed of celiac disease (CD with increased intraepithelial duodenal infiltration, being classified as lymphocytic enteritis, Marsh I type. She was put on a gluten-free diet (GFD, having lost 6 kg of weight after 6 months, with a good control of DM-II and presenting a significant clinical improvement. It is rewarding to search the presence of two coincidental metabolic diseases associated to OI, specially CD, because of the dramatic clinical benefit in the general found after putting on a GFD.

  8. 成骨不全的临床及X线表现分析%Analysis of the clinical manifestation of osteogenesis imperfecta and its X-ray images

    Institute of Scientific and Technical Information of China (English)

    杨建松

    2014-01-01

    目的:探讨成骨不全的临床X线表现及其病因。方法:回顾性分析4例成骨不全病例,所有病例均行X线检查。结果:4例均表现为蓝色巩膜,肢体畸形,X线表现为长骨及肋骨多发性骨折,颅骨骨化不全。结论:当遇到新生儿及小儿蓝色巩膜,肢体畸形,进行性听力障碍,应想到成骨不全的可能性。%Objective:To investigate the clinical X-ray manifestation of osteogenesis imperfecta and its pathogeny.Methods:Retrospective analyze 4 patients with osteogenesis imperfect.All the cases underwent X-ray examination.Results:4 cases all characterized by blue sclera,limb deformity,and the X-ray showed multiple long bone and fractured ribs,skull ossification incomplete.Conclusion:When we treated on the neonatal and pediatric blue sclera,limb deformity,progressive hearing impairment, we should think of the possibility of osteogenesis imperfecta.

  9. Osteogenesis imperfecta Type I caused by a novel mutation in the start codon of the COL1A1 gene in a Korean family.

    Science.gov (United States)

    Cho, Sung Yoon; Lee, Ji-Ho; Ki, Chang-Seok; Chang, Mi Sun; Jin, Dong-Kyu; Han, Heon-Seok

    2015-01-01

    Osteogenesis imperfecta (OI) comprises a heterogeneous group of disorders characterized by susceptibility to bone fractures ranging in severity from perinatal death to a subtle increase in fracture frequency. We report the case of a patient who appeared healthy at birth and did not experience any fractures until 12 months of age. We observed blue sclera, frequent fractures without commensurate trauma, nearly normal stature, the absence of dentinogenesis imperfecta, no bony deformity, and no limitation of mobility in the patient--all characteristics suggestive of OI Type I. The patient's mother also had blue sclera and a history of frequent fracture episodes until the age of 15 years. A novel COL1A1 missense mutation (c.2T>G) disrupting the start codon of the gene (ATG to AGG (Met1Arg)) was found in the patient and his mother.

  10. Bone geometry, density, and microarchitecture in the distal radius and tibia in adults with osteogenesis imperfecta type I assessed by high-resolution pQCT

    DEFF Research Database (Denmark)

    Folkestad, Lars; Hald, Jannie Dahl; Hansen, Stinus

    2012-01-01

    Osteogenesis Imperfecta (OI) is a hereditary disorder characterized by decreased biosynthesis or impaired morphology of collagen type-1 that leads to decreased bone mass and increased bone fragility. We hypothesized that patients with OI have altered bone microstructure and bone geometry. In this...... treated with bisphosphonates. HR-pQCT at the distal radius and distal tibia and dual-energy X-ray absorptiomentry of total hip, femoral neck, trochanteric region and the lumbar spine (L1-L4) were performed. The patients were shorter than the controls (159¿±¿10¿cm vs. 170¿±¿9¿cm, p¿...

  11. Skeletal phenotypes in adult patients with osteogenesis imperfecta-correlations with COL1A1/COL1A2 genotype and collagen structure

    DEFF Research Database (Denmark)

    Hald, J D; Folkestad, L; Harsløf, T

    2016-01-01

    Osteogenesis imperfecta (OI) is characterized by a high fracture rate and great heterogeneity. This cross-sectional study presents skeletal investigations and protein analyses in 85 adult OI patients. We find significant differences in bone mass, architecture, and fracture rate that correlate well...... of this study was to improve our understanding of clinical manifestations by investigating anthropometry and skeletal phenotypes (DXA, HRpQCT) in an adult OI population and compare the findings to underlying COL-1 genotype and structure. METHODS: The study comprised 85 OI patients aged 45 (19-78) years...

  12. Results of a bone splint technique for the treatment of lower limb deformities in children with type I osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Dasheng Lin

    2013-01-01

    Full Text Available Background: Children with osteogenesis imperfecta (OI can suffer from frequent fractures and limb deformities, resulting in impaired ambulation. Osteopenia and thin cortices complicate orthopedic treatment in this group. This study evaluates the clinical results of a bone splint technique for the treatment of lower limb deformities in children with type I OI. The technique consists of internal plating combined with cortical strut allograft fixation. Materials and Methods: We prospectively followed nine children (five boys, four girls with lower limb deformities due to type I OI, who had been treated with the bone splint technique (11 femurs, four tibias between 2003 and 2006. The fracture healing time, deformity improvement, ambulation ability and complications were recorded to evaluate treatment effects. Results: At the time of surgery the average age in our study was 7.7 years (range 5-12 years. The average length of followup was 69 months (range 60-84 months. All patients had good fracture healing with an average healing time of 14 weeks (range 12-16 weeks and none experienced further fractures, deformity, or nonunion. The fixation remained stable throughout the procedure in all cases, with no evidence of loosening or breakage of screws and the deformity and mobility significantly improved after surgery. Of the two children confined to bed before surgery, one was able to walk on crutches and the other needed a wheelchair. The other seven patients could walk without walking aids or support like crutches. Conclusions: These findings suggest that the bone splint technique provides good mechanical support and increases the bone mass. It is an effective treatment for children with OI and lower limb deformities.

  13. Molecular Consequences of the SERPINH1/HSP47 Mutation in the Dachshund Natural Model of Osteogenesis Imperfecta.

    Science.gov (United States)

    Lindert, Uschi; Weis, Mary Ann; Rai, Jyoti; Seeliger, Frank; Hausser, Ingrid; Leeb, Tosso; Eyre, David; Rohrbach, Marianne; Giunta, Cecilia

    2015-07-17

    Osteogenesis imperfecta (OI) is a heritable connective tissue disease characterized by bone fragility and increased risk of fractures. Up to now, mutations in at least 18 genes have been associated with dominant and recessive forms of OI that affect the production or post-translational processing of procollagen or alter bone homeostasis. Among those, SERPINH1 encoding heat shock protein 47 (HSP47), a chaperone exclusive for collagen folding in the ER, was identified to cause a severe form of OI in dachshunds (L326P) as well as in humans (one single case with a L78P mutation). To elucidate the disease mechanism underlying OI in the dog model, we applied a range of biochemical assays to mutant and control skin fibroblasts as well as on bone samples. These experiments revealed that type I collagen synthesized by mutant cells had decreased electrophoretic mobility. Procollagen was retained intracellularly with concomitant dilation of ER cisternae and activation of the ER stress response markers GRP78 and phospho-eIF2α, thus suggesting a defect in procollagen processing. In line with the migration shift detected on SDS-PAGE of cell culture collagen, extracts of bone collagen from the OI dog showed a similar mobility shift, and on tandem mass spectrometry, the chains were post-translationally overmodified. The bone collagen had a higher content of pyridinoline than control dog bone. We conclude that the SERPINH1 mutation in this naturally occurring model of OI impairs how HSP47 acts as a chaperone in the ER. This results in abnormal post-translational modification and cross-linking of the bone collagen.

  14. Development of a high-throughput resequencing array for the detection of pathogenic mutations in osteogenesis imperfecta.

    Directory of Open Access Journals (Sweden)

    Yao Wang

    Full Text Available Osteogenesis imperfecta (OI is a rare inherited skeletal disease, characterized by bone fragility and low bone density. The mutations in this disorder have been widely reported to be on various exonal hotspots of the candidate genes, including COL1A1, COL1A2, CRTAP, LEPRE1, and FKBP10, thus creating a great demand for precise genetic tests. However, large genome sizes make the process daunting and the analyses, inefficient and expensive. Therefore, we aimed at developing a fast, accurate, efficient, and cheaper sequencing platform for OI diagnosis; and to this end, use of an advanced array-based technique was proposed.A CustomSeq Affymetrix Resequencing Array was established for high-throughput sequencing of five genes simultaneously. Genomic DNA extraction from 13 OI patients and 85 normal controls and amplification using long-range PCR (LR-PCR were followed by DNA fragmentation and chip hybridization, according to standard Affymetrix protocols. Hybridization signals were determined using GeneChip Sequence Analysis Software (GSEQ. To examine the feasibility, the outcome from new resequencing approach was validated by conventional capillary sequencing method.Overall call rates using resequencing array was 96-98% and the agreement between microarray and capillary sequencing was 99.99%. 11 out of 13 OI patients with pathogenic mutations were successfully detected by the chip analysis without adjustment, and one mutation could also be identified using manual visual inspection.A high-throughput resequencing array was developed that detects the disease-associated mutations in OI, providing a potential tool to facilitate large-scale genetic screening for OI patients. Through this method, a novel mutation was also found.

  15. A method distinguishing expressed vs. null mutations of the Col1A1 gene in osteogenesis imperfecta

    Energy Technology Data Exchange (ETDEWEB)

    Redford-Badwal, D.A.; Stover, M.L.; McKinstry, M. [and others

    1994-09-01

    Osteogenesis imperfecta (OI) is a heterogeneous group of heritable disorders of bone characterized by increased susceptibility to fracture. Most of the causative mutations were identified in patients with the lethal form of the disease. Attention is now shifting to the milder forms of OI where glycine substitutions and null producing mutations have been found. Single amino acid substitutions can be identified by RT/PCR of total cellular RNA, but this approach does not work well for null mutations since the defective transcript does not accumulate in the cytoplasm. We have altered our RNA extraction method to separate RNA from the nuclear and cytoplasmic compartments of cultured fibroblasts. Standard methods of mutation identification (RT/PCR followed by SSCP) is applied to each RNA fraction. DNA from an abnormal band on the SSCP gel is eluted and amplified by PCR for cloning and sequencing. Using this approach we have identified an Asp to Asn change in exon 50 (type II OI) and a Gly to Arg in exon 11 (type I OI) of the COL1A1 gene. These changes were found in both nuclear and cytoplasmic compartments. These putative mutations are currently being confirmed by protein studies. In contrast, three patients with mild OI associated with reduced {proportional_to}(I)mRNA, had distinguishing SSCP bands present in the nuclear but not the cytoplasmic compartment. In one case a frame shift mutation was observed, while the other two revealed polymorphisms. The compartmentalization of the mutant allele has directed us to look elsewhere in the transcript for the causative mutation. This approach to mutation identification is capable of distinguishing these fundamentally different types of mutations and allows for preferential cloning and sequencing of the abnormal allele.

  16. Osteogenesis imperfecta: Ultrastructural and histological findings on examination of skin revealing novel insights into genotype-phenotype correlation.

    Science.gov (United States)

    Balasubramanian, M; Sobey, G J; Wagner, B E; Peres, L C; Bowen, J; Bexon, J; Javaid, M K; Arundel, P; Bishop, N J

    2016-01-01

    Osteogenesis imperfecta (OI) is a heterogeneous group of inherited disorders of bone formation, resulting in low bone mass and an increased propensity to fracture. Over 90% of patients with OI have a mutation in COL1A1/COL1A2, which shows an autosomal dominant pattern of inheritance. In-depth phenotyping and in particular, studies involving manifestations in the skin connective tissue have not previously been undertaken in OI. The aims of the study were to perform histological and ultrastructural examination of skin biopsies in a cohort of patients with OI; to identify common and distinguishing features in order to inform genotype-phenotype correlation; and to identify common and distinguishing features between the different subtypes of OI. As part of the RUDY (Rare Diseases in Bone, Joints and/or Blood Vessels) study, in collaboration with the NIHR Rare Diseases Translational Research Collaboration, we undertook a national study of skin biopsies in patients with OI. We studied the manifestations in the skin connective tissue and undertook in-depth clinical and molecular phenotyping of 16 patients with OI. We recruited 16 patients: analyses have shown that in type 1 collagen mutation positive patients (COL1A1/ COL1A2) (n-4/16) consistent findings included: variable collagen fibril diameter (CFD) and presence of collagen flowers. Histological examination in these patients showed an increase in elastic fibers that are frequently fragmented and clumped. These observations provide evidence that collagen flowers and CFD variability are consistent features in OI due to type 1 collagen defects and reinforce the need for accurate phenotyping in conjunction with genomic analyses.

  17. Effect of high-dose vitamin D supplementation on bone density in youth with osteogenesis imperfecta: A randomized controlled trial.

    Science.gov (United States)

    Plante, Laura; Veilleux, Louis-Nicolas; Glorieux, Francis H; Weiler, Hope; Rauch, Frank

    2016-05-01

    Osteogenesis imperfecta (OI) is a heritable condition characterized by fragile bones. Our previous studies indicated that serum 25-hydroxyvitamin D (25OHD) concentrations were positively associated with lumbar spine areal bone mineral density (LS-aBMD) in children and adolescents with OI. Here we assessed whether one year of high-dose vitamin D supplementation results in higher LS-aBMD z-scores in youth with OI. A one-year double-blind randomized controlled trial conducted at a pediatric orthopedic hospital in Montreal, Canada. Sixty patients (age: 6.0 to 18.9years; 35 female) were randomized in equal numbers to receive either 400 or 2000international units (IU) of vitamin D, stratified according to baseline bisphosphonate treatment status and pubertal stage. At baseline, the average serum 25OHD concentration was 65.6nmol/L (SD 20.4) with no difference between treatment groups (p=0.77); 21% of patients had results <50nmol/L. Vitamin D supplementation was associated with higher serum 25OHD concentrations in 90% of participants. The increase in mean 25OHD was significantly higher (p=0.02) in the group receiving 2000IU of vitamin D (mean [95% CI]=30.5nmol/L [21.3; 39.6]) than in the group receiving 400IU (15.2nmol/L [6.4; 24.1]). No significant differences in LS-aBMD z-score changes were detected between treatment groups. Thus, supplementation with vitamin D at 2000IU increased serum 25OHD concentrations in children with OI more than supplementation with 400IU. However, in this study where about 80% of participants had baseline serum 25OHD concentrations ≥50nmol/L, this difference had no detectable effect on LS-aBMD z-scores.

  18. Identification and molecular characterization of two novel mutations in COL1A2 in two Chinese families with osteogenesis imperfecta

    Institute of Scientific and Technical Information of China (English)

    Zhenping Xu; Yulei Li; Xiangyang Zhang; Fanming Zeng; Mingxiong Yuan; Mugen Liu; Qing Kenneth Wang; Jing Yu Liu

    2011-01-01

    Osteogenesis imperfecta (OI, also known as brittle bone disease) is caused mostly by mutations in two type Ⅰ collagen genes, COL1A1 and COL1A2 encoding the pro-α1 (Ⅰ) and pro-α2 (Ⅰ) chains of type Ⅰ collagen, respectively. Two Chinese families with autosomal dominant OI were identified and characterized. Linkage analysis revealed linkage of both families to COL1A2 on chromosome 7q21.3-q22.1. Mutational analysis was carried out using direct DNA sequence analysis. Two novel missense mutations, c.3350A>G and c.3305G>C, were identified in exon 49 of COL1A2 in the two families, respectively. The c.3305G>C mutation resulted in substitution of a glycine residue (G) by an alanine residue (A) at codon 1102 (p.G1102A), which was found to be mutated into serine (S), argine (R), aspartic acid (D), or valine (V) in other families. The c.3350A>G variant may be a de novo mutation resulting in p.Y1117C. Both mutations co-segregated with OI in respective families, and were not found in 100 normal controls. The G1102 and Y1117 residues were evolutionarily highly conserved from zebrafish to humans. Mutational analysis did not identify any mutation in the COX-2 gene (a modifier gene of OI). This study identifies two novel mutations p.G1102A and p.Y1117C that cause OI, significantly expands the spectrum of COL1A2 mutations causing OI, and has a significant implication in prenatal diagnosis of OI.

  19. Impairment of diastolic function in adult patients affected by osteogenesis imperfecta clinically asymptomatic for cardiac disease: casuality or causality?

    Science.gov (United States)

    Migliaccio, Silvia; Barbaro, Giuseppe; Fornari, Rachele; Di Lorenzo, Gabriella; Celli, Mauro; Lubrano, Carla; Falcone, Stefania; Fabbrini, Elisa; Greco, Emanuela; Zambrano, Anna; Brama, Marina; Prossomariti, Giancarlo; Marzano, Sara; Marini, Mario; Conti, Francesco; D'Eufemia, Patrizia; Spera, Giovanni

    2009-01-09

    Osteogenesis imperfecta (OI) is a rare inherited connective disorder causing increased bone fragility and low bone mass. OI includes severe bone fragility, impaired dentinogenesis, with less common alterations in the joints, blood vessels, heart valves, skin. Interestingly, description of left ventricular rupture, aortic dissection and heart valves incompetence has been previously described. Death may occur in OI patients for cardiac disease in asyntomatic subjects. Aim of our study has been to evaluate the presence of potential subclinical cardiac disorders and to characterize cardiac functional parameters by echocardiography in adults with OI in absence of cardiac symptoms. Forty patients (21 females and 19 males) affected by type I, III, IV OI and 40 control subjects (20 females and 20 males) were evaluated in the study. Patients and controls underwent clinical examination, screening for endocrine and metabolic disorders, 12-lead electrocardiogram and echocardiogram. In particular, all subjects were evaluated by two-dimensional echocardiography with continuous- and pulse-wave Doppler. Patients and controls belonged to NYHA class I and no significant electrocardiographic alteration was documented in both groups. Thirty-eight patients (95%) showed valvular regurgitation compared to one control subject (2.5%; Prelaxation time (IRT) was increased by 47% (95% CI: 26% to 53%; Pmetabolic alterations. These diastolic echocardiographic parameters might worsen over time, especially if other cardiovascular risk factors (e.g., smoking, hypertension, metabolic and endocrine alterations) are not carefully checked, monitored and treated. In the context of a multidisciplinary evaluation of OI patients, our data suggest that a careful cardiological evaluation of these patients is indicated beside skeletal evaluation and therapeutical skeletal options.

  20. Mutations in SEC24D, encoding a component of the COPII machinery, cause a syndromic form of osteogenesis imperfecta.

    Science.gov (United States)

    Garbes, Lutz; Kim, Kyungho; Rieß, Angelika; Hoyer-Kuhn, Heike; Beleggia, Filippo; Bevot, Andrea; Kim, Mi Jeong; Huh, Yang Hoon; Kweon, Hee-Seok; Savarirayan, Ravi; Amor, David; Kakadia, Purvi M; Lindig, Tobias; Kagan, Karl Oliver; Becker, Jutta; Boyadjiev, Simeon A; Wollnik, Bernd; Semler, Oliver; Bohlander, Stefan K; Kim, Jinoh; Netzer, Christian

    2015-03-05

    As a result of a whole-exome sequencing study, we report three mutant alleles in SEC24D, a gene encoding a component of the COPII complex involved in protein export from the ER: the truncating mutation c.613C>T (p.Gln205(∗)) and the missense mutations c.3044C>T (p.Ser1015Phe, located in a cargo-binding pocket) and c.2933A>C (p.Gln978Pro, located in the gelsolin-like domain). Three individuals from two families affected by a similar skeletal phenotype were each compound heterozygous for two of these mutant alleles, with c.3044C>T being embedded in a 14 Mb founder haplotype shared by all three. The affected individuals were a 7-year-old boy with a phenotype most closely resembling Cole-Carpenter syndrome and two fetuses initially suspected to have a severe type of osteogenesis imperfecta. All three displayed a severely disturbed ossification of the skull and multiple fractures with prenatal onset. The 7-year-old boy had short stature and craniofacial malformations including macrocephaly, midface hypoplasia, micrognathia, frontal bossing, and down-slanting palpebral fissures. Electron and immunofluorescence microscopy of skin fibroblasts of this individual revealed that ER export of procollagen was inefficient and that ER tubules were dilated, faithfully reproducing the cellular phenotype of individuals with cranio-lentico-sutural dysplasia (CLSD). CLSD is caused by SEC23A mutations and displays a largely overlapping craniofacial phenotype, but it is not characterized by generalized bone fragility and presented with cataracts in the original family described. The cellular and morphological phenotypes we report are in concordance with the phenotypes described for the Sec24d-deficient fish mutants vbi (medaka) and bulldog (zebrafish).

  1. Pre- and postnatal transplantation of fetal mesenchymal stem cells in osteogenesis imperfecta: a two-center experience.

    Science.gov (United States)

    Götherström, Cecilia; Westgren, Magnus; Shaw, S W Steven; Aström, Eva; Biswas, Arijit; Byers, Peter H; Mattar, Citra N Z; Graham, Gail E; Taslimi, Jahan; Ewald, Uwe; Fisk, Nicholas M; Yeoh, Allen E J; Lin, Ju-Li; Cheng, Po-Jen; Choolani, Mahesh; Le Blanc, Katarina; Chan, Jerry K Y

    2014-02-01

    Osteogenesis imperfecta (OI) can be recognized prenatally with ultrasound. Transplantation of mesenchymal stem cells (MSCs) has the potential to ameliorate skeletal damage. We report the clinical course of two patients with OI who received prenatal human fetal MSC (hfMSC) transplantation and postnatal boosting with same-donor MSCs. We have previously reported on prenatal transplantation for OI type III. This patient was retransplanted with 2.8 × 10(6) same-donor MSCs per kilogram at 8 years of age, resulting in low-level engraftment in bone and improved linear growth, mobility, and fracture incidence. An infant with an identical mutation who did not receive MSC therapy succumbed at 5 months despite postnatal bisphosphonate therapy. A second fetus with OI type IV was also transplanted with 30 × 10(6) hfMSCs per kilogram at 31 weeks of gestation and did not suffer any new fractures for the remainder of the pregnancy or during infancy. The patient followed her normal growth velocity until 13 months of age, at which time longitudinal length plateaued. A postnatal infusion of 10 × 10(6) MSCs per kilogram from the same donor was performed at 19 months of age, resulting in resumption of her growth trajectory. Neither patient demonstrated alloreactivity toward the donor hfMSCs or manifested any evidence of toxicities after transplantation. Our findings suggest that prenatal transplantation of allogeneic hfMSCs in OI appears safe and is of likely clinical benefit and that retransplantation with same-donor cells is feasible. However, the limited experience to date means that it is not possible to be conclusive and that further studies are required.

  2. A novel mutation in LEPRE1 that eliminates only the KDEL ER- retrieval sequence causes non-lethal osteogenesis imperfecta.

    Directory of Open Access Journals (Sweden)

    Masaki Takagi

    Full Text Available Prolyl 3-hydroxylase 1 (P3H1, encoded by the LEPRE1 gene, forms a molecular complex with cartilage-associated protein (CRTAP and cyclophilin B (encoded by PPIB in the endoplasmic reticulum (ER. This complex is responsible for one step in collagen post-translational modification, the prolyl 3-hydroxylation of specific proline residues, specifically α1(I Pro986. P3H1 provides the enzymatic activity of the complex and has a Lys-Asp-Glu-Leu (KDEL ER-retrieval sequence at the carboxyl terminus. Loss of function mutations in LEPRE1 lead to the Pro986 residue remaining unmodified and lead to slow folding and excessive helical post-translational modification of type I collagen, which is seen in both dominant and recessive osteogenesis imperfecta (OI. Here, we present the case of siblings with non-lethal OI due to novel compound heterozygous mutations in LEPRE1 (c.484delG and c.2155dupC. The results of RNA analysis and real-time PCR suggest that mRNA with c.2155dupC escapes from nonsense-mediated RNA decay. Without the KDEL ER- retrieval sequence, the product of the c.2155dupC variant cannot be retained in the ER. This is the first report of a mutation in LEPRE1 that eliminates only the KDEL ER-retrieval sequence, whereas other functional domains remain intact. Our study shows, for the first time, that the KDEL ER- retrieval sequence is essential for P3H1 functionality and that a defect in KDEL is sufficient for disease onset.

  3. The phenotypic features of osteogenesis imperfecta resulting from a mutation of the carboxyl-terminal pro alpha 1(I) propeptide that impairs the assembly of type I procollagen and formation of the extracellular matrix

    NARCIS (Netherlands)

    Cole, WG; Chow, CW; Bateman, JF; Sillence, DO

    1996-01-01

    The features of a baby with lethal perinatal osteogenesis imperfecta (OI-II), resulting from the substitution of tryptophan 94 by cysteine in the carboxyl-terminal propeptide of pro alpha 1(I) chains of type I procollagen, were studied. The limbs and torso were of normal length, shape, and proportio

  4. Mutation in a gene for type I procollagen (COL1A2) in a woman with postmenopausal osteoporosis: Evidence for phenotypic and genotypic overlap with mild osteogenesis imperfecta

    Energy Technology Data Exchange (ETDEWEB)

    Spotila, L.D.; Constantinou, C.D.; Sereda, L.; Ganguly, A.; Prockop, D.J. (Jefferson Medical College, Philadelphia, PA (United States)); Riggs, B.L. (Mayo Clinic, Rochester, MN (United States))

    1991-06-15

    Mutations in the two genes for type I collagen (COL1A1 or COL1A2) cause osteogenesis imperfecta (OI), a heritable disease characterized by moderate to extreme brittleness of bone early in life. Here, the authors show that a 52-year-old post menopausal woman with severe osteopenia and a compression fracture of a thoracic vertebra had a mutation in the gene for the {alpha}2(I) chain of type I collagen (COL1A2) similar to mutations that cause OI. cDNA was prepared from the woman's skin fibroblast RNA and assayed for the presence of a mutation by treating DNA heteroduplexes with carbodiimide. The results indicated a sequence variation in the region encoding amino acid residues 660-667 of the {alpha}2(I) chain. Further analysis demonstrated a single-base mutation that caused a serine-for-glycine substitution at position 661 of the {alpha}2(I) triple-helical domain. The substitution produced posttranslational overmodification of the collagen triple helix, as is seen with most glycine substitutions that cause OI. The patient had a history of five previous fractures, slightly blue sclerae, and slight hearing loss. Therefore, the results suggest that there may be phenotypic and genotypic overlap between mild osteogenesis imperfecta and postmenopausal osteoporosis, and that a subset of women with postmenopausal osteoporosis may have mutations in the genes for type I procollagen.

  5. Dentinogenesis imperfecta: A case report

    Directory of Open Access Journals (Sweden)

    Subramaniam P

    2008-06-01

    Full Text Available Dentinogenesis imperfecta is an autosomal dominant disorder of tooth development characterized by the presence of opalescent dentin, resulting in a dusky blue to brownish discoloration of the teeth. This condition is genetically and clinically heterogeneous; it may affect only the teeth or it may be associated with the osteogenesis imperfecta. Dentinogenesis imperfecta has been subdivided into three types: type I is associated with osteogenesis imperfecta; in type II there is no associated osteogenesis imperfecta; and when the condition is associated with the Brandywine triracial isolate and large pulp chambers it is classified as type III. This report describes a 16-year-old female patient who showed the characteristic dental features of dentinogenesis imperfecta type II. The etiology and prevalence of the disorder, and a comprehensive treatment plan, will be briefly reviewed.

  6. Dentinogenesis imperfecta: a case report.

    Science.gov (United States)

    Subramaniam, P; Mathew, S; Sugnani, S N

    2008-06-01

    Dentinogenesis imperfecta is an autosomal dominant disorder of tooth development characterized by the presence of opalescent dentin, resulting in a dusky blue to brownish discoloration of the teeth. This condition is genetically and clinically heterogeneous; it may affect only the teeth or it may be associated with the osteogenesis imperfecta. Dentinogenesis imperfecta has been subdivided into three types: type I is associated with osteogenesis imperfecta; in type II there is no associated osteogenesis imperfecta; and when the condition is associated with the Brandywine triracial isolate and large pulp chambers it is classified as type III. This report describes a 16-year-old female patient who showed the characteristic dental features of dentinogenesis imperfecta type II. The etiology and prevalence of the disorder, and a comprehensive treatment plan, will be briefly reviewed.

  7. The influence of ibandronate treatment on bone density and biochemical bone markers in patients with osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Ingmar Ipach

    2012-09-01

    Full Text Available Osteogenesis imperfecta (OI is characterized by different signs including increased bone fragility, short stature, blue sclera, abnormal tooth growth and often secondary immobility. No curative therapy has been found for this rare disease up to now, and different pharmacological substances have been tried as treatment for severe forms of OI. Promising results were seen with intravenous bisphosphonates in the treatment of patients with OI. The aim of present study was to show the effect of intravenous ibandronate therapy on bone density and bone metabolism markers. We analyzed the data of 27 patients with the diagnosis of OI who were treated off-label with intravenous ibandronate. Ibandronate was administered by intravenous infusion every three months at a dosage of 0.3-2 mg. Bone turnover markers and bone density were measured before starting therapy and every three months during treatment. Bone density was measured by using an ultrasound imaging system providing an accurate image of the calcaneus and by evaluating broadband ultrasound attenuation (BUA. Twenty-seven patients were treated with intravenous iban- dronate during the observation period. 18 were female. The mean age of all patients was 23.9 years ± 19.6 (range 4-63. Seventeen patients were categorized to have OI Type I, 5 patients to have OI Type III and 5 patients to have OI Type IV. There was a statistically significant decrease in total alkaline phosphatase (P<0.0001. We detected also a statistically significant decrease in the ratio urinary deoxypyridinoline/urinary creatinine (P=0.0048 and the ratio urinary pyridinoline/urinary creatinine (P<0.0001 respectively. There was also a statistically significant increase in serum magnesium (P=0.034 and BUA (P=0.0071. No statistically significant changes were seen for total serum calcium (P=0.16, the ratio of urine calcium/urine creatinine (P=0.29, alkaline phosphatase (isoform bone (P=0.3, procollagen-I-peptide (P=0.5, osteocalcin (P=0

  8. Involving Families with Osteogenesis Imperfecta in Health Service Research: Joint Development of the OI/ECE Questionnaire.

    Directory of Open Access Journals (Sweden)

    Maman Joyce Dogba

    Full Text Available Despite the growing interest in understanding the psycho-social impact of rare genetic diseases, few studies examine this concept and even fewer seek to obtain feedback from families who have lived the experience. The aim of this project was to involve families of children living with osteogenesis imperfecta (OI in the development of a tool to assess the impact of OI on the lives of patients and their families.This project used an integrated knowledge translation approach in which knowledge users (clinicians and people living with OI and their families were consulted throughout the four steps of development, that is: content mapping, item generation, tool appraisal and pre-testing of the questionnaires. The International Classification of Functioning and Health was used as a framework for content mapping. Based on a scoping review we selected two validated tools to use as a basis for developing the questionnaire. The final parent self-report version measured six domains: experience of diagnosis; use of health services; use of social and psychological support services; expectations about tertiary specialized centers; and socio-demographic information.A total of 27 out of 40 families receiving care at the Shriners Hospital for Children-Canada and invited to participate in the pre-test returned the completed questionnaires. In more than two-thirds of families (69%; n = 18 OI was suspected either at or within the first 3 months after birth. Up to 46% of families consulted between 3 and 5 doctors (46%; n = 12 prior to final diagnosis. The use of services by families varied from 0 to 16 consultations, 0 to 9 exploratory examinations and 1 to 10 types of allied health services. In the 12 months prior to the study, fewer than a quarter of children had been admitted, for treatment, for hospital stays of longer than 8 hours or to an emergency department (24% and 9% respectively. Only 29% of parents received psychological support.This joint development

  9. Four patients with Sillence type I osteogenesis imperfecta and mild bone fragility, complicated by left ventricular cardiac valvular disease and cardiac tissue fragility caused by type I collagen mutations

    DEFF Research Database (Denmark)

    Vandersteen, Anthony M; Lund, Allan M; Ferguson, David J P

    2014-01-01

    Osteogenesis imperfecta (OI) type I is a hereditary disorder of connective tissue (HDCT) characterized by blue or gray sclerae, variable short stature, dentinogenesis imperfecta, hearing loss, and recurrent fractures from infancy. We present four examples of OI type I complicated by valvular heart...... disease and associated with tissue fragility. The diagnosis of a type I collagen disorder was confirmed by abnormal COL1A1 or COL1A2 gene sequencing. One patient was investigated with electrophoresis of collagens from cultured skin fibroblasts, showing structurally abnormal collagen type I, skin biopsy...

  10. Complicações hemorrágicas intracranianas na osteogênese imperfeita Intracranial hemorrhagic complications in cases of osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Laertel F. Fassoni

    1968-09-01

    Full Text Available São descritas complicações hemorrágicas intracranianas em dois pacientes com osteogênese imperfeita. Sangramento espontâneo ocorreu no espaço subaracnóideo em um dos pacientes e no espaço subdural, no outro. Os achados clínicos e paraclínicos são discutidos à luz de um distrbio mesenquimatoso difuso semelhante ao que caracteriza as demais moléstias hereditárias do mesênquima.The intracranial hemorrhagic complications in two patients with osteogenesis imperfecta are described. Spontaneous bleeding into the subarachnoid space occurred in one patient and into the subdural space in another. The clinical findings and their relationship to a generalized disturbance of mesenchymal tissue are discussed.

  11. Ⅰ型成骨不全一家系的分子诊断%Molecular diagnosis of a Chinese pedigree with osteogenesis imperfecta type Ⅰ

    Institute of Scientific and Technical Information of China (English)

    柯龙凤; 郑林文; 谢海花; 严爱贞; 朱忠勇; 兰风华

    2009-01-01

    Objective To perform molecular diagnosis for a Chinese pedigree with osteogenesis imperfecta type Ⅰ.Methods Thirty pairs of primers were designed tO amplify all the 52 exons,exon boundaries and promoter region of the COL1A1 gene from genomic DNA of peripheral blood cells of the family members.The PCR products were purified and directly sequenced.To check the mutation in normal controls.the genomic DNA from peripheral blood cells of the index patient,his mother and 60 normal controls were analyzed by amplification refractory mutation system.ResultsA missense mutation of GAT >CAT was identified at codon 1441 of the COL1A1 gene from the family,which resulted in the replacement of aspartic acid by histidine(D1441H).This mutation was not found in a group of 60 normal controls.Conclusion The method for molecular diagnosis of osteogenesis imperfecta was established and a novel COL1A1 gene mutation,D1441H,was identified in the Chinese pedigree with osteogenesis imperfecta type Ⅰ.%目的 对Ⅰ型成骨不全(osteogenesis imperfecta,OI)1个家系进行分子诊断.方法 从先证者的基因组DNA人手,自行设计30对引物,扩增产物涵盖全部COL1A1基因52个外显子及启动子区域,并以相应引物对PCR产物进行直接测序.针对突变位点,设计扩增阻滞突变系统(amplification refractory mutation system,ARMS)引物,在60名无关对照中进行突变筛查.结果 在先证者的其中1条COL1A1等位基因上存在突变,即COL1A1基因第1441位(位于第52外显子,P30)发生了GAT→CAT改变.使原来编码的天冬氨酸被组氨酸取代(D1441H);其母亲的其中1条COL1A1等位基因上也存在相同突变,而正常对照相应的COL1A1基因序列与GenBank参考序列相同.ARMS分析显示,在60个无关对照中均未检测到D1441H突变.查阅国内外相关文献及COL1A1基因突变数据库,未发现有关COL1A1基因D1441H突变的报道.结论 建立了基于COL1A1基因突变分析的成骨不全分子诊断方法 ,

  12. 1 case of osteogenesis imperfecta combined with the fracture in the femoral shaft%成骨不全症合并股骨干骨折一例

    Institute of Scientific and Technical Information of China (English)

    于文超; 李刚

    2012-01-01

    @@ 临床资料 女性,24岁,2010年12月2日因轻微外伤致左大腿肿痛、畸形、活动受限2h就诊,查体:患者智力发育正常,听力良好,语言清楚.头颅大小正常,双眼巩膜呈浅蓝色(图1),牙齿发育良好,脊柱发育正常.左大腿中上段肿胀畸形明显,压痛,可扪及异常活动及骨擦感,下肢纵向叩击痛阳性.X线片示:骨盆扁平、不对称,脊柱骨质及形态未见明显异常,双侧股骨干变形,略向外方凸,皮质增厚,左股骨干中上段骨折,骨折线为横形,移位明显.%Osteogenesis imperfecta (OI) is an autosomal dominant disorder due to the obstruction in the formation of collagen type I, which is featured with the increase of the degree of bone fragility. Major manifestations in clinic: bone fragility, blue sclerae, hearing loss and mild-moderate skeletal deformity. 1 case of osteogenesis imperfecta combined with the fracture in the femoral shaft underwent open reduction, locked plate fixation and bone grafting in clinic, with good postoperative recovery.

  13. An X -ray Diagnosis of Osteogenesis Imperfecta (report of 2 cases)%成骨不全症的X线诊断(附2例报告)

    Institute of Scientific and Technical Information of China (English)

    赵朝伦; 徐国铭

    2014-01-01

    Objective:The purpose of a literature review of X -ray diagnosis of osteogenesis imperfecta .Methods:A retrospective a-nalysis of two cases of children with osteogenesis imperfecta diagnosed as clinical and X -ray findings .Results : This composition in children with osteogenesis imperfecta Osteoporosis bone universality , see different periods of long bone fractures , backbone bending de-formation , including one case of rib rear deformation front of enlargement , spinal vertebral compression double concave deformation or flat , pelvic deformity .Conclusion:X -ray diagnosis of osteogenesis imperfecta have certain characteristics , provide an important basis for clinical diagnosis .Combination of clinical and X -ray features , and a variety of osteoporotic bone disease identification .%目的:结合文献复习成骨不全症的X线诊断。方法:回顾性分析2例确诊成骨不全症患儿的临床和X线表现。结果:本组成骨不全症患儿骨骼普遍性骨质疏松,长骨见不同时期骨折,骨干弯曲变形,其中1例肋骨后部变形,前端膨大,脊柱椎体双凹变形或压缩变扁,骨盆畸形。结论:X线诊断成骨不全症有一定的特征,为临床提供重要诊断依据。结合临床及X线特点,可以和多种骨质疏松性骨病鉴别。

  14. Osteogenesis Imperfecta Foundation

    Science.gov (United States)

    ... Week Fine Wines Strong Bones Bone China Tea Blue Jeans for Better Bones Calendar Online Store What is ... 1 - 2 - 3! Click beloew for information about Blue Jeans for Better Bones, Bone China Tea, and more! ...

  15. 常染色体隐性遗传性成骨不全症的分子遗传学研究进展%Advances on molecular genetics of autosomal recessive osteogenesis imperfecta

    Institute of Scientific and Technical Information of China (English)

    曹丽华; 张学

    2010-01-01

    成骨不全症(osteogenesis imperfecta,OI)又称脆骨症,由于遗传缺陷而引起Ⅰ型胶原结构或功能异常,表现为全身骨骼等结缔组织异常.临床特点是多发性骨折,同时可伴有巨头畸形、蓝巩膜、耳聋、牙齿改变和脊柱后侧凸等.成骨不全症不仪临床表型变异度大,而且遗传异质性高,以常染色体显件或隐性遗传方式传递,本文就常染色体隐性遗传性成骨不全症的分子遗传学研究进展加以综述.%Osteogenesis imperfecta (OI) , also known as brittle bone disease, is a genetic disorder of connective tissue caused by structural or functional abnormality of type I collagen. OI is characterized by multiple bone fractures. Affected individuals may also have macrocephaly, blue sclerae,hearing loss, dentinogene-sis imperfecta, and kyphoscoliosis. OI shows marked clinical variability and genetic heterogeneity, and both autosomal dominant and recessive forms exist. In this paper, we will review the recent progress in molecular genetics of the autosomal recessive OI.

  16. In vitro sulfate turnover in osteogenesis imperfacta congenita and tarda

    Energy Technology Data Exchange (ETDEWEB)

    Delvin, E.E.; Glorieux, F.H.; Lopez, E.

    1979-01-01

    Sulfate (/sup 35/SO/sub 4//sup -2/) uptake was studied in confluent skin fibroblasts from three patients with osteogenesis imperfecta congenita, six patients with osteogenesis imperfecta tarda, three clinically unaffected relatives of an osteogenesis imperfecta tarda patient, and four controls. Only two of the osteogenesis imperfecta congenita cell strains showed an increased uptake of sulfate, all other cell strains being comparable to the control group. The degradation rate of glycosaminolgycans in mutants as seen by the chase experiments was comparable to that found in the normal control cell strains. Glucose oxidation was normal in the osteogenesis imperfecta cell strains having an abnormal sulfate uptake. This rules out the possibility of an hypermetabolic state of these cells. These findings do not warrant the use of /sup 35/SO/sub 4//sup -2/ incorporation in cultured cells as a tool for prenatal diagnosis of osteogenesis imperfecta.

  17. An N-terminal glycine to cysteine mutation in the collagen COL1A1 gene produces moderately severe osteogenesis imperfecta

    Energy Technology Data Exchange (ETDEWEB)

    Wilcox, W.; Scott, L.; Cohn, D. [Cedars-Sinai Medical Center, Los Angeles, CA (United States)

    1994-09-01

    Osteogenesis imperfecta (OI) is usually due to mutations in the type I procollagen genes COL1A1 and COL1A2. Point mutations close to the N-terminus are generally milder than those near the C-terminus of the molecule (the gradient hypothesis of collagen mutations). We describe a patient with moderately severe OI due to a mutation in the N-terminal portion of the triple helical domain of the {alpha}1(I) chain. Electrophoretic analysis of collagen isolated from fibroblast cultures suggested the abnormal presence of a cysteine in the N-terminal portion of the {alpha}1(I) chain. Five overlapping DNA fragments amplified from fibroblast RNA were screened for mutations using single strand conformational polymorphism (SSCP) and heteroduplex analyses. Direct DNA sequence analysis of the single positive fragment demonstrated a G to T transversion, corresponding to a glycine to cysteine substitution at position 226 of the triple helical domain of the {alpha}1(I) chain. The mutation was confirmed by restriction enzyme analysis of amplified genomic DNA. The mutation was not present in fibroblasts from either phenotypically normal parent. Combining this mutation with other reported mutations, glycine to cysteine substitutions at positions 205, 211, 223, and 226 produce a moderately severe phenotype whereas flanking mutations at positions 175 and 382 produce a mild phenotype. This data supports a regional rather than a gradient model of the relationship between the nature and location of type I collagen mutations and OI phenotype.

  18. 双膦酸盐治疗成骨不全症的研究进展%Bisphosphonate in the treatment of osteogenesis imperfecta

    Institute of Scientific and Technical Information of China (English)

    韩兰稳; 李梅

    2011-01-01

    Osteogenesis imperfecta(OI) is a heritable disease characterized by bone fragility and reduced bone mass,which can lead to multiple fractures in the patients and result in serious skeletal deformity.Genetic researches have demonstrated that OI mainly resulted from mutations of the genes encoding collagen type Ⅰ.No effective drugs for OI is avmlable previously.However,current clinical studies indicate that bisphosphonate can improve life quality of patients with OI through inhibiting osteoclast-induced bone resorption,increasing bone mineral density,decreasing bone fracture rates,and alleviating pain.%成骨不全症是以骨骼脆性增加和骨量减少为特征的一种遗传性疾病,可导致患者反复发生骨折,致畸率和致残率较高.该疾患主要由重要的骨基质蛋白Ⅰ型胶原编码基因突变所致.以往成骨不全症缺乏有效治疗药物,近年来临床研究显示双膦酸盐类药物能够有效抑制破骨细胞介导的骨吸收,增加成骨不全症患者的骨密度,降低骨折发生率,缓解骨痛,提高患者生活质量.

  19. A case of fetal osteogenesis imperfecta type 2A: longitudinal observation of natural course in utero and pitfalls for prenatal ultrasound diagnosis.

    Science.gov (United States)

    Kimura, Ibuki; Araki, Ryota; Yoshizato, Toshiyuki; Miyamoto, Shingo

    2015-10-01

    We present a case of osteogenesis imperfecta (OI) type 2A in which a natural course in utero was observed from 23 weeks' gestation to term. At 23 weeks' gestation, a sonographic examination showed a cloverleaf skull-like head, a narrow thorax, and marked shortening of the long bones with bowing of the femurs and humeri. Follow-up examinations showed that the cloverleaf skull-like head was not evident at 28 weeks' gestation. Discontinuity of the ribs and femurs was observed at 26 and 30 weeks' gestation, respectively. This finding suggested bone fractures, which were confirmed by three-dimensional computed tomography at 32 weeks' gestation. Ultrasonographic findings of bones, including the long bones and calvarium, changed with advancing gestation during the second trimester. Characteristic features of OI type 2A were evident during the late second to early third trimesters. Repeated ultrasonographic examinations together with three-dimensional computed tomography are necessary for the definitive diagnosis of OI type 2A in the second trimester.

  20. Targeted exome sequencing identifies novel compound heterozygous mutations in P3H1 in a fetus with osteogenesis imperfecta type VIII.

    Science.gov (United States)

    Huang, Yanru; Mei, Libin; Lv, Weigang; Li, Haoxian; Zhang, Rui; Pan, Qian; Tan, Hu; Guo, Jing; Luo, Xiaomei; Chen, Chen; Liang, Desheng; Wu, Lingqian

    2017-01-01

    Osteogenesis imperfecta (OI) is a highly clinically and genetically heterogeneous group of disorders. It is difficult to identify severe OI in the perinatal period. Here, a Chinese woman with a suspected history of fetal OI was referred to our institution at 19weeks of gestation, due to ultrasound inspection during antenatal screening, which revealed bulbous metaphyses, short humeri, and short thick bent femora in the fetus. Using targeted exome sequencing of 248 genes known to be involved in skeletal system diseases, we identified novel compound heterozygous mutation in the P3H1 gene in the fetus with OI type VIII: c.105_120del (p.D36Rfs*16) and c.2164C>T (p.Q722*). These two mutations were inherited from the father and mother, respectively. The mRNA level of P3H1 wasn't changed suggested that mRNA with this mutation escaped from nonsense-mediated RNA decay. Besides, the level of P3H1 was absence while the CRTAP was mildly decreased. In conclusion, our findings imply this novel compound heterozygous mutation as the molecular pathogenetic in a Chinese fetus with OI type VIII, and demonstrate that targeted next-generation sequencing (NGS) is an accurate, rapid, and cost-effective method in the genetic diagnosis of fetal skeletal dysplasia with genetic and clinical heterogeneity, especially for autosomal recessive skeletal disorders.

  1.  Mutations of noncollagen genes in osteogenesis imperfecta – implications of the gene products in collagen biosynthesis and pathogenesis of disease

    Directory of Open Access Journals (Sweden)

    Anna Galicka

    2012-06-01

    Full Text Available  Recent investigations revealed that the “brittle bone” phenotype in osteogenesis imperfecta (OI is caused not only by dominant mutations in collagen type I genes, but also by recessively inherited mutations in genes responsible for the post-translational processing of type I procollagen as well as for bone formation. The phenotype of patients with mutations in noncollagen genes overlaps with very severe type III and lethal type II OI caused by mutations in collagen genes. Mutations in genes that encode proteins involved in collagen prolyl 3-hydroxylation (P3H1/CRTAP/CyPB eliminated Pro986 hydroxylation and caused an increase in modification of collagen helix by prolyl 4-hydroxylase and lysyl hydroxylase. However, the importance of these disturbances in the disease pathomechanism is not known. Loss of complex proteins’ function as collagen chaperones may dominate the disease mechanism. The latest findings added to the spectrum of OI-causing and collagen-influencing factors other chaperones (HSP47 and FKBP65 and protein BMP-1, which emphasizes the complexity of collagen folding and secretion as well as their importance in bone formation. Furthermore, mutations in genes encoding transcription factor SP7/Osterix and pigment epithelium-derived factor (PEDF constitute a novel mechanism for OI, which is independent of changes in biosynthesis and processing of collagen.

  2. 二膦酸盐在成骨不全疾病中的应用%Bisphosphonate in the treatment of osteogenesis imperfecta

    Institute of Scientific and Technical Information of China (English)

    王熙然; 裴育; 窦京涛; 陆菊明

    2009-01-01

    Osteogenesis imperfecta (oI) is a genetic disease of connective tissue.The most serous consequences are bone fractures and deformities.90% patients with OI is caused by type I collagen gene mutation.Clinical research indicates that bisphosphonates can inhibit bone resorption,improve bone mass,decrease the incidence of fracture and improve quality of life.Bisphosphonates is an effective treatment for OI.This paper will outline the role of bisphosphonates in mechanism,treatment,effects,side effects and other problems.%成骨不全是一种以脆骨症为典型特征的遗传性结缔组织疾病,该病最严重的后果为骨脆弱所导致的频繁骨折、继发性骨骼畸形,90%的成骨不伞是I型胶原基因突变所致.临床研究证实,二膦酸盐可抑制破骨细胞活性,增加骨密度、降低骨折发生率、改善患者生活质量,是目前内科对成骨不全治疗的有效手段.本文就二膦酸盐的作用机制、治疗方法、疗效、不良反应及存在的问题等予以综述.

  3. Premature chain termination is a unifying mechanism for COL1A1 null alleles in osteogenesis imperfecta type I cell strains

    Energy Technology Data Exchange (ETDEWEB)

    Willing, M.C.; Deschenes, S.P.; Roberts, E.J. [Univ. of Iowa, Iowa City, IA (United States)] [and others

    1996-10-01

    Nonsense and frameshift mutations, which predict premature termination of translation, often cause a dramatic reduction in the amount of transcript from the mutant allele (nonsense-mediated mRNA decay). In some genes, these mutations also influence RNA splicing and induce skipping of the exon that contains the nonsense codon. To begin to dissect how premature termination alters the metabolism of RNA from the COL1A1 gene, we studied nonsense and frameshift mutations distributed over exons 11-49 of the gene. These mutations were originally identified in 10 unrelated families with osteogenesis imperfecta (OI) type I. We observed marked reduction in steady-state amounts of mRNA from the mutant allele in both total cellular and nuclear RNA extracts of cells from affected individuals, suggesting that nonsense-mediated decay of COL1A1 RNA is a nuclear phenomenon. Position of the mutation within the gene did not influence this observation. None of the mutations induced skipping of either the exon containing the mutation or, for the frameshifts, the downstream exons with the new termination sites. Our data suggest that nonsense and frameshift mutations throughout most of the COL1A1 gene result in a null allele, which is associated with the predictable mild clinical phenotype, OI type I. 42 refs., 6 figs., 1 tab.

  4. Identification of a novel COL1A1 frameshift mutation, c.700delG, in a Chinese osteogenesis imperfecta family.

    Science.gov (United States)

    Wang, Xiran; Pei, Yu; Dou, Jingtao; Lu, Juming; Li, Jian; Lv, Zhaohui

    2015-03-01

    Osteogenesis imperfecta (OI) is a family of genetic disorders associated with bone loss and fragility. Mutations associated with OI have been found in genes encoding the type I collagen chains. People with OI type I often produce insufficient α1-chain type I collagen because of frameshift, nonsense, or splice site mutations in COL1A1 or COL1A2. This report is of a Chinese daughter and mother who had both experienced two bone fractures. Because skeletal fragility is predominantly inherited, we focused on identifying mutations in COL1A1 and COL1A2 genes. A novel mutation in COL1A1, c.700delG, was detected by genomic DNA sequencing in the mother and daughter, but not in their relatives. The identification of this mutation led to the conclusion that they were affected by mild OI type I. Open reading frame analysis indicated that this frameshift mutation would truncate α1-chain type I collagen at residue p263 (p.E234KfsX264), while the wild-type protein would contain 1,464 residues. The clinical data were consistent with the patients' diagnosis of mild OI type I caused by haploinsufficiency of α1-chain type I collagen. Combined with previous reports, identification of the novel mutation COL1A1-c.700delG in these patients suggests that additional genetic and environmental factors may influence the severity of OI.

  5. Substitution of cysteine for glycine at residue 415 of one allele of the alpha 1(I) chain of type I procollagen in type III/IV osteogenesis imperfecta.

    Science.gov (United States)

    Nicholls, A C; Oliver, J; Renouf, D V; Keston, M; Pope, F M

    1991-01-01

    We have examined the type I collagen in a patient with type III/IV osteogenesis imperfecta. Two forms of alpha 1(I) chain were produced, one normal and the other containing a cysteine residue within the triple helical domain of the molecule. Cysteine is not normally present in this domain of type I collagen. Peptide mapping experiments localised the mutation to peptide alpha 1(I)CB3 which spans residues 403 to 551 of the triple helix. Subsequent PCR amplification of cDNA covering this region followed by sequencing showed a G to T single base change in the GGC codon for glycine 415 generating TGC, the codon for cysteine. The effect of the mutation on the protein is to delay secretion from the cell, reduce the thermal stability of the molecule by 2 degrees C, and cause excessive post-translational modification of all chains in molecules containing one or more mutant alpha 1(I) chains. The clinical phenotype observed in this patient and the position of the mutation conform to the recent prediction of Starman et al that Gly----Cys mutations in the alpha 1(I) chain have a gradient of severity decreasing from the C-terminus to the N-terminus. Images PMID:1770532

  6. Augmentation of the mandible via a "tent-pole" procedure and implant treatment in a patient with type III osteogenesis imperfecta: clinical and histologic considerations.

    Science.gov (United States)

    Wannfors, Karin; Johansson, Carina; Donath, Karl

    2009-01-01

    The present report describes the oral rehabilitation of a female patient suffering from type III osteogenesis imperfecta. Agenesis of the mandibular anterior teeth and malocclusion caused partly by heavily worn teeth made dental rehabilitation necessary. Before a decision to use implants following a grafting procedure, the osseointegration of microimplants was tested. After 4 and 12 months, bone plugs containing two microimplants were retrieved from the patient. Histologic evaluation showed very sparse/poor osseointegration, and the healing time seemed to be much longer than normal. A decision was made to use the "tent-pole" procedure described by Marx et al, followed by prolonged healing. Surgery was uneventful, and the patient was provided with four implants that were partly covered with bone obtained from the iliac crest. Platelet-rich plasma was used to accelerate bone healing. After 9 months, the implants were uncovered and the prosthetic construction was completed. The implant-supported metal-ceramic restoration was serving well at the 1-year and 3-year follow-ups. Minimal resorption of marginal bone was detected during the first year.

  7. Qualitative research on the psychological feeling of mothers of children with osteogenesis imperfecta during treatment%成骨不全患儿母亲对治疗过程心理感受的质性研究

    Institute of Scientific and Technical Information of China (English)

    刘旭艳; 任秀智; 陈玉霞; 刘西芬; 房凤岭

    2015-01-01

    Objective To understand the feeling of mothers of children with osteogenesis imperfecta during the accompany of children's diagnosis and treatment.Methods A total of 20 mothers of children with osteogenesis imperfecta participated the semi-structured interview.The data were analyzed by Colaizzi's method of phenomenology.Results Three themes were acquired including heavy psychological burden,facing multiple pressure and mother's support through analysis,reorganization and extraction of the subjects.Conclusions Mothers of children with osteogenesis imperfecta needed humanistic concern and emotional support.Nursers should adopted personalized care measures to improve their quality of life.%目的 了解成骨不全患儿的母亲在陪伴患儿诊断、治疗过程中的心理感受.方法 通过半结构访谈形式访问了20名成骨不全患儿的母亲,将获得的资料通过Colaizzi现象学研究法进行分析、整理.结果 通过分析、整理和提炼主题,得出心理负担重、面临多重压力、母亲的支持力量3个主题.结论 成骨不全患儿母亲需要深切人文关怀和情感支持,护理人员应采取个性化的护理措施,以提高其母亲生活质量.

  8. Substitution of arginine for glycine at position 154 of the {alpha}1 chain of type I collagen in a variant of osteogenesis imperfecta: Comparison to previous cases with the same mutation

    Energy Technology Data Exchange (ETDEWEB)

    Zhuang, J.; Tromp, G.; Kuivaniemi, H.; Prockop, D.J. [Thomas Jefferson Univ., Philadelphia, PA (United States); Castells, S. [Univ. Hospital of Brooklyn, NY (United States)

    1996-01-11

    A substitution of arginine for glycine at amino acid position 154 of the {alpha}1(I) collagen chain was found in a father and his three children. The phenotype of the patients includes manifestations of types I and III/IV osteogenesis imperfecta, but appears to be milder than that of the previously described two unrelated patients that had the identical mutation in the {alpha}1(I) collagen chain. The variability in the phenotype raises the possibility of epistatic loci or environmental effects on expression of the disorder. 35 refs., 3 figs., 2 tabs.

  9. Defective Proteolytic Processing of Fibrillar Procollagens and Prodecorin Due to Biallelic BMP1 Mutations Results in a Severe, Progressive Form of Osteogenesis Imperfecta.

    Science.gov (United States)

    Syx, Delfien; Guillemyn, Brecht; Symoens, Sofie; Sousa, Ana Berta; Medeira, Ana; Whiteford, Margo; Hermanns-Lê, Trinh; Coucke, Paul J; De Paepe, Anne; Malfait, Fransiska

    2015-08-01

    Whereas the vast majority of osteogenesis imperfecta (OI) is caused by autosomal dominant defects in the genes encoding type I procollagen, mutations in a myriad of genes affecting type I procollagen biosynthesis or bone formation and homeostasis have now been associated with rare autosomal recessive OI forms. Recently, homozygous or compound heterozygous mutations in BMP1, encoding the metalloproteases bone morphogenetic protein-1 (BMP1) and its longer isoform mammalian Tolloid (mTLD), were identified in 5 children with a severe autosomal recessive form of OI and in 4 individuals with mild to moderate bone fragility. BMP1/mTLD functions as the procollagen carboxy-(C)-proteinase for types I to III procollagen but was also suggested to participate in amino-(N)-propeptide cleavage of types V and XI procollagens and in proteolytic trimming of other extracellular matrix (ECM) substrates. We report the phenotypic characteristics and natural history of 4 adults with severe, progressive OI characterized by numerous fractures, short stature with rhizomelic shortening, and deformity of the limbs and variable kyphoscoliosis, in whom we identified novel biallelic missense and frameshift mutations in BMP1. We show that BMP1/mTLD-deficiency in humans not only results in delayed cleavage of the type I procollagen C-propeptide but also hampers the processing of the small leucine-rich proteoglycan prodecorin, a regulator of collagen fibrillogenesis. Immunofluorescent staining of types I and V collagen and transmission electron microscopy of the dermis show impaired assembly of heterotypic type I/V collagen fibrils in the ECM. Our study thus highlights the severe and progressive nature of BMP1-associated OI in adults and broadens insights into the functional consequences of BMP1/mTLD-deficiency on ECM organization.

  10. Absence of the ER Cation Channel TMEM38B/TRIC-B Disrupts Intracellular Calcium Homeostasis and Dysregulates Collagen Synthesis in Recessive Osteogenesis Imperfecta.

    Directory of Open Access Journals (Sweden)

    Wayne A Cabral

    2016-07-01

    Full Text Available Recessive osteogenesis imperfecta (OI is caused by defects in proteins involved in post-translational interactions with type I collagen. Recently, a novel form of moderately severe OI caused by null mutations in TMEM38B was identified. TMEM38B encodes the ER membrane monovalent cation channel, TRIC-B, proposed to counterbalance IP3R-mediated Ca2+ release from intracellular stores. The molecular mechanisms by which TMEM38B mutations cause OI are unknown. We identified 3 probands with recessive defects in TMEM38B. TRIC-B protein is undetectable in proband fibroblasts and osteoblasts, although reduced TMEM38B transcripts are present. TRIC-B deficiency causes impaired release of ER luminal Ca2+, associated with deficient store-operated calcium entry, although SERCA and IP3R have normal stability. Notably, steady state ER Ca2+ is unchanged in TRIC-B deficiency, supporting a role for TRIC-B in the kinetics of ER calcium depletion and recovery. The disturbed Ca2+ flux causes ER stress and increased BiP, and dysregulates synthesis of proband type I collagen at multiple steps. Collagen helical lysine hydroxylation is reduced, while telopeptide hydroxylation is increased, despite increased LH1 and decreased Ca2+-dependent FKBP65, respectively. Although PDI levels are maintained, procollagen chain assembly is delayed in proband cells. The resulting misfolded collagen is substantially retained in TRIC-B null cells, consistent with a 50-70% reduction in secreted collagen. Lower-stability forms of collagen that elude proteasomal degradation are not incorporated into extracellular matrix, which contains only normal stability collagen, resulting in matrix insufficiency. These data support a role for TRIC-B in intracellular Ca2+ homeostasis, and demonstrate that absence of TMEM38B causes OI by dysregulation of calcium flux kinetics in the ER, impacting multiple collagen-specific chaperones and modifying enzymes.

  11. Bone geometry, density, and microarchitecture in the distal radius and tibia in adults with osteogenesis imperfecta type I assessed by high-resolution pQCT.

    Science.gov (United States)

    Folkestad, Lars; Hald, Jannie Dahl; Hansen, Stinus; Gram, Jeppe; Langdahl, Bente; Abrahamsen, Bo; Brixen, Kim

    2012-06-01

    Osteogenesis imperfecta (OI) is a hereditary disorder characterized by decreased biosynthesis or impaired morphology of type I collagen that leads to decreased bone mass and increased bone fragility. We hypothesized that patients with OI have altered bone microstructure and bone geometry. In this cross-sectional study we compared patients with type I OI to age- and gender-matched healthy controls. A total of 39 (13 men and 26 women) patients with OI, aged 53 (range, 21-77) years, and 39 controls, aged 53 (range, 21-77) years, were included in the study. Twenty-seven of the patients had been treated with bisphosphonates. High-resolution peripheral quantitative computed tomography (HR-pQCT) at the distal radius and distal tibia and dual-energy X-ray absorptiometry of total hip, femoral neck, trochanteric region, and the lumbar spine (L1-L4) were performed. The patients were shorter than the controls (159 ± 10 cm versus 170 ± 9 cm, p radius (p radius, total bone area was 5% lower in OI than in controls (p radius and tibia the number of trabeculae was lower in patients compared to the controls (35% and 38%, respectively, p radius (p < 0.001 at both sites) when compared with controls. We conclude that patients with type I OI have lower aBMD, vBMD, bone area, and trabecular number when compared with healthy age- and gender-matched controls.

  12. Local amino acid sequence patterns dominate the heterogeneous phenotype for the collagen connective tissue disease Osteogenesis Imperfecta resulting from Gly mutations.

    Science.gov (United States)

    Xiao, Jianxi; Yang, Zhangfu; Sun, Xiuxia; Addabbo, Rayna; Baum, Jean

    2015-10-01

    Osteogenesis Imperfecta (OI), a hereditary connective tissue disease in collagen that arises from a single Gly → X mutation in the collagen chain, varies widely in phenotype from perinatal lethal to mild. It is unclear why there is such a large variation in the severity of the disease considering the repeating (Gly-X-Y)n sequence and the uniform rod-like structure of collagen. We systematically evaluate the effect of local (Gly-X-Y)n sequence around the mutation site on OI phenotype using integrated bio-statistical approaches, including odds ratio analysis and decision tree modeling. We show that different Gly → X mutations have different local sequence patterns that are correlated with lethal and nonlethal phenotypes providing a mechanism for understanding the sensitivity of local context in defining lethal and non-lethal OI. A number of important trends about which factors are related to OI phenotypes are revealed by the bio-statistical analyses; most striking is the complementary relationship between the placement of Pro residues and small residues and their correlation to OI phenotype. When Pro is present or small flexible residues are absent nearby a mutation site, the OI case tends to be lethal; when Pro is present or small flexible residues are absent further away from the mutation site, the OI case tends to be nonlethal. The analysis also reveals the dominant role of local sequence around mutation sites in the Major Ligand Binding Regions that are primarily responsible for collagen binding to its receptors and shows that non-lethal mutations are highly predicted by local sequence considerations alone whereas lethal mutations are not as easily predicted and may be a result of more complex interactions. Understanding the sequence determinants of OI mutations will enhance genetic counseling and help establish which steps in the collagen hierarchy to target for drug therapy.

  13. Scoliosis in osteogenesis imperfecta caused by COL1A1/COL1A2 mutations - genotype-phenotype correlations and effect of bisphosphonate treatment.

    Science.gov (United States)

    Sato, Atsuko; Ouellet, Jean; Muneta, Takeshi; Glorieux, Francis H; Rauch, Frank

    2016-05-01

    Bisphosphonates are widely used to treat children with osteogenesis imperfecta (OI), a bone fragility disorder that is most often caused by mutations in COL1A1 or COL1A2. However, it is unclear whether this treatment decreases the risk of developing scoliosis. We retrospectively evaluated spine radiographs and charts of 437 patients (227 female) with OI caused by mutations in COL1A1 or COL1A2 and compared the relationship between scoliosis, genotype and bisphosphonate treatment history. At the last follow-up (mean age 11.9 [SD: 5.9] years), 242 (55%) patients had scoliosis. The prevalence of scoliosis was highest in OI type III (89%), followed by OI type IV (61%) and OI type I (36%). Moderate to severe scoliosis (Cobb angle ≥25°) was rare in individuals with COL1A1 haploinsufficiency mutations but was present in about two fifth of patients with triple helical glycine substitutions or C-propeptide mutations. During the first 2 to 4years of bisphosphonate therapy, patients with OI type III had lower Cobb angle progression rates than before bisphosphonate treatment, whereas in OI types I and IV bisphosphonate treatment was not associated with a change in Cobb angle progression rates. At skeletal maturity, the prevalence of scoliosis (Cobb angle >10°) was similar in patients who had started bisphosphonate treatment early in life (before 5.0years of age) and in patients who had started therapy later (after the age of 10.0years) or had never received bisphosphonate therapy. Bisphosphonate treatment decreased progression rate of scoliosis in OI type III but there was no evidence of a positive effect on scoliosis in OI types I and IV. The prevalence of scoliosis at maturity was not influenced by the bisphosphonate treatment history in any OI type.

  14. The severity of Osteogenesis imperfecta and type I collagen pattern in human skin as determined by nonlinear microscopy: proof of principle of a diagnostic method.

    Directory of Open Access Journals (Sweden)

    Javier Adur

    Full Text Available BACKGROUND: The confirmatory diagnosis of Osteogenesis Imperfecta (OI requires invasive, commonly bone biopsy, time consuming and destructive methods. This paper proposes an alternative method using a combination of two-photon excitation fluorescence (TPEF and second-harmonic generation (SHG microscopies from easily obtained human skin biopsies. We show that this method can distinguish subtypes of human OI. METHODOLOGY/PRINCIPAL FINDINGS: Different aspects of collagen microstructure of skin fresh biopsies and standard H&E-stained sections of normal and OI patients (mild and severe forms were distinguished by TPEF and SHG images. Moreover, important differences between subtypes of OI were identified using different methods of quantification such as collagen density, ratio between collagen and elastic tissue, and gray-level co-occurrence matrix (GLCM image-pattern analysis. Collagen density was lower in OI dermis, while the SHG/autofluorescence index of the dermis was significantly higher in OI as compared to that of the normal skin. We also showed that the energy value of GLCM texture analysis is useful to discriminate mild from severe OI and from normal skin. CONCLUSIONS/SIGNIFICANCE: This work demonstrated that nonlinear microscopy techniques in combination with image-analysis approaches represent a powerful tool to investigate the collagen organization in skin dermis in patients with OI and has the potential to distinguish the different types of OI. The procedure outlined in this paper requires a skin biopsy, which is almost painless as compared to the bone biopsy commonly used in conventional methods. The data presented here complement existing clinical diagnostic techniques and can be used as a diagnostic procedure to confirm the disease, evaluate its severity and treatment efficacy.

  15. Corrective osteotomy for the treatment of femoral deformity in children with osteogenesis imperfecta%成骨不全股骨畸形的截骨矫形

    Institute of Scientific and Technical Information of China (English)

    张鹏; 王延宙; 张敏刚; 王恒冰; 王继孟

    2010-01-01

    目的 探讨多段截骨矫形治疗成骨不全儿童股骨畸形的手术特点和临床效果.方法 2004年1月至2007年1月,采用多段截骨矫形+Rush钉内固定,治疗成骨不全股骨畸形10例(共14根股骨).其中男7例,女3例,年龄5~16岁,平均年龄10.3岁.术后进行临床评价(活动方式、股骨长度和感染)和放射学评价(Rush钉的位置、移位、弯曲、断裂和再骨折).结果 随访3~5年,平均3.5年,所有病例均骨性愈合,愈合时间6~9周,平均7周;首次手术的平均年龄为6.1岁,4例需要二次手术更换Rush钉;首次与第二次手术的时间间隔为1.5~4年,平均2.7年.所有病例未发生骨折、血管神经损伤、感染、骨不连等并发症;股骨畸形和下肢功能获得明显改善(P<0.01).其中1例未及时更换Rush钉.其远端自骨干穿出,局部成角畸形,给予截骨矫形、更换Rush钉后治愈.结论 术前个性化设计,采取多段截骨矫形治疗成骨不全儿童的股骨畸形,可以加速骨愈合,减少再骨折;最大可能的矫正畸形,改善下肢功能,提高生活质量.%Objective To evaluate the surgical strategies and outcomes of multiple corrective osteotomy for the treatment of femoral deformity in children with osteogenesis imperfecta.Methods Between 2004 and 2007,14 femora of 10 patients with osteogenesis imperfect,who underwent recurrent fractures and/or deformities in the femora at this center,were recruited in this study.They included 7 males and 3 females,aged from 5 to 16 years old(mean age,10.3 years old).The femoral deformities were corrected by multiple corrective osteotomy and Rush pins.After surgery,the clinical conditions of these patients regarding mobility status,growth and limb-length,and infection were followed up.Radiological images were taken to monitor pin placement,migration,bending,breakage of pins,and refracture of femora.Results The average duration of follow-up was 3.5 years(ranged from 3 to 5 years).Union was

  16. 一罕见成骨不全IV型的基因诊断%Gene diagnosis of a rare case with osteogenesis imperfecta type IV

    Institute of Scientific and Technical Information of China (English)

    郭奕斌; 艾阳; 蒋玮莹

    2013-01-01

    Objective The gene diagnosis of a child with suspected OI-IV (Osteogenesis Imperfecta type IV) or other types of diseases was made to reveal the internal cause of morbidity and frequent bone fracture, which creates the indispensable precondition for the prenatal gene diagnosis and symptomatic treatment in the future. Methods According to the observation of symptoms, signs and X-ray testing, the child was diagnosed preliminarily with OI-IV or other types. Then extracting DNA from peripheral blood, PCR-DNA direct sequencing were applied to detect the COL1A1 gene, and the mutation was analyzed and identified. Results A classical missense mutation (c.823G>C/p.G275R) was found in the coding region of COL1A1 gene, which was confirmed a known mutation leading to OI-IV by HGMD. Conclusion The proband is a rare patient child suffered with OI-IV. The mutation of p.G275R is a pathological mutation first reported in China.%  目的对一疑似成骨不全IV型或其他类型的患儿实施基因诊断,以揭示患儿发病及频繁骨折的内在原因,为今后实施对症治疗和产前基因诊断创造必要的前提条件.方法对经症状、体征观察和X线检查初诊为成骨不全IV型或其他类型的患儿,在抽取外周血制备DNA模板后,采用PCR、DNA直接测序法,对患儿的COL1A1基因进行突变检测,然后对所发现的突变进行分析和鉴定.结果在COL1A1基因的编码区内发现一典型的错义突变(c.823G>C1/p.G275R),经查HGMD数据库证实为成骨不全IV型的致病性突变.结论先证者为一罕见的成骨不全IV型患儿,所发现的p.G275R突变为中国人群首次报道的病理性突变.

  17. Intubação nasotraqueal guiada por rinoscópio em criança de um ano de idade portadora de Osteogenesis imperfecta: relato de caso Intubación nasotraqueal guiada por rinoscopio en niño de un año de edad portador de Osteogenesis imperfecta: relato de caso Rhinoscope-guided nasotracheal intubation in a one-year old child with Osteogenesis imperfecta: case report

    Directory of Open Access Journals (Sweden)

    Eduardo Toshiyuki Moro

    2009-10-01

    de esa enfermedad asociada a la hidrocefalia, y sometido a la anestesia venosa total e intubación nasotraqueal, guiada por rinoscopio para la realización de la derivación ventrículo-peritoneal. RELATO DEL CASO: Paciente del sexo masculino, un año y tres meses de edad, con diagnósticos de OI (tipo III e hidrocefalia sometido a la derivación ventrículo-peritoneal. Después de la administración de midazolam (1 mg.kg-1 por vía oral, 30 minutos antes del procedimiento, el niño fue monitorizado, con posterior venoclisis con catéter 24G. Después de la oxigenación, se procedió a la inducción anestésica con remifentanil, propofol y cisatracurio. La intubación nasotraqueal fue guiada por rinolaringoscopio (Olimpus® ENF P3 y cánula de 4,5 mm con balón e insertada sin intercurrencias. La anestesia se mantuvo con infusión de remifentanil y propofol. La operación duró 120 minutos sin intercurrencias. CONCLUSIONES: El presente relato describió una alternativa de acceso a la vía aérea en niños sometidos a la anestesia general y que por algún motivo no pueden ser ventilados a través de la máscara laríngea. El rinolaringoscopio, por presentar un diámetro reducido, permite la inserción de cánulas traqueales que no podrían ser utilizadas con el uso del fibroscopio convencional.BACKGROUND AND OBJECTIVES: Osteogenesis imperfecta (OI is a rare, autosomal dominant disease. Anesthesia for patients with OI has several challenges; among them, management of the airways and the choice of anesthetic technique should be mentioned. The objective of this report was to describe the case of a child with this disorder associated with hydrocephalus who underwent total intravenous anesthesia and rhinoscope-guided nasotracheal intubation for a ventriculoperitoneal shunt. CASE REPORT: This is a 15-month old male with OI (type III and hydrocephalus who underwent placement of a ventriculoperitoneal shunt. After the oral administration of midazolam (1 mg.kg-1 30 minutes

  18. Dentinogenesis imperfecta in adults with osteogenesis imperfecta

    DEFF Research Database (Denmark)

    Gjørup, Hans; Hald, Jannie Dahl; Schmidt, Malene;

    . In the evaluation of the dental hard tissues, signs of obliteration of pulp chambers, reduced length of roots, presence of pulp stones, taurodontism, and cervical constriction were assessed. Results: Among a total of 72 patients with OI, 20 (27.8 %) had DI. Obliteration and cervical constriction were frequently...... of Medical Endocrinology, Denmark. A clinical examination and a full-mouth periapical survey with digital intraoral radiographs using GX 1000 dental X-ray©, as well as a digital panoramic radiograph using the digital radiographic equipment Planmeca Promax© were performed. Patients had clinical photos taken...

  19. 一例成骨不全Ⅱ型高危胎儿的产前基因诊断%Prenatal gene diagnosis of a high-risk fetus with osteogenesis imperfecta type Ⅱ

    Institute of Scientific and Technical Information of China (English)

    艾阳; 唐佳; 方群; 吴晓昀; 郭奕斌

    2011-01-01

    目的 对广东一疑似致死性侏儒症或成骨不全Ⅱ型的高危胎儿实施产前基因诊断,以阐明胎儿骨发育异常的真实病因,及时预防患胎出生.方法 对经超声检查初诊为致死性侏儒症或成骨不全、已孕25周的高危胎儿,在抽取脐血制备DNA模板后,采用PCR-DNA直接测序法,分别对胎儿的FGFR3基因和COL1A1基因进行突变检测,然后对所发现的突变进行分析和鉴定.结果 FGFR3基因未发现病理性突变,而COL1A1基因发现一典型的杂合错义突变(c.3065 G>T,PG1022V),经查HGMD数据库证实为成骨不全Ⅱ型的致病性突变.结论 (1)此高危胎儿为成骨不全Ⅱ型患胎,应及时终止妊娠(胎儿已经引产,经复查证实与产前基因诊断结果完全一致).(2)在超声初诊基础上,采用产前基因诊断可快速、有效对高危胎儿做出确诊,为出生缺陷的预防提供技术保障.%Objective To clarify the real pathogeny of the dysostoses of fetuses ,the prenatal gene diagnosis of a Guangdong high-risk fetus suspected with osteogenesis imperfecta type II or thanatophoric dwarfism was carried out, which stopped the birth of the suffering fetuses. Methods The high-risk fetus of 25 weeks was preliminarily diagnosed with thanatophoric dwarfism or osteogenesis imperfecta by ultrasonic test. The cord blood was extracted to make preparation for DNA template ,PCR-DNA sequencing was used to detect the mutation of FGFR3 gene and COL1A1 gene,then the mutations were analyzed and identified. Results There was no pathological mutation on the FGFR3 gene. There was a c. 3065 G > T,p. G1022V heterozygosis missense mutation on the COL1A1 gene,which caused osteogenesis imperfecta type II ;it was already reported on the HGMD. Conclusions (1) The high-risk fetus suffer with osteogenesis imperfecta -Ⅱ ,which should be induced labour (the fetus had been induced labour already. The result of prenatal gene diagnosis was completely accordance with the result of

  20. Two cases of osteogenesis imperfecta complicated with ankylosing spondylitis and review of literature%成骨不全合并强直性脊柱炎2例并文献复习

    Institute of Scientific and Technical Information of China (English)

    刘剑雯

    2014-01-01

    迄今尚未有成骨不全(osteogenesis imperfecta,OI)合并强直性脊柱炎(ankylosing spondylitis,AS)的报道,该家系2例患者同时患有成骨不全和强直性脊柱炎,复习文献发现成骨不全和强直性脊柱炎在骨质改变方面均存在骨密度减低的特征性病变。近年来越来越多的研究表明经典Wnt信号通路在调节成骨细胞功能及骨形成中发挥重要的作用,并且其均参与成骨不全及强直性脊柱炎的发病过程。本文结合本病例特点,同时联系临床和文献报道,对Wnt信号通路在成骨不全及强直性脊柱炎发病过程中的可能作用进行讨论。%Hitherto no cases about osteogenesis imperfecta (OI) complicated with ankylosing spondylitis (AS) have been reported. In this article we present two patients diagnosed with OI and AS from one family. Both OI and AS are characterized by decreased bone mineral density (BMD). In recent years, more and more research has been revealing the key role of classic Wnt singal pathway in regulating osteoblasts function and bone formation. Reviewing literatures and features of these two cases, we will discuss about Wnt signal pathway in pathogenic development of OI and AS.

  1. Four patients with Sillence type I osteogenesis imperfecta and mild bone fragility, complicated by left ventricular cardiac valvular disease and cardiac tissue fragility caused by type I collagen mutations.

    Science.gov (United States)

    Vandersteen, Anthony M; Lund, Allan M; Ferguson, David J P; Sawle, Philip; Pollitt, Rebecca C; Holder, Susan E; Wakeling, Emma; Moat, Neil; Pope, F Michael

    2014-02-01

    Osteogenesis imperfecta (OI) type I is a hereditary disorder of connective tissue (HDCT) characterized by blue or gray sclerae, variable short stature, dentinogenesis imperfecta, hearing loss, and recurrent fractures from infancy. We present four examples of OI type I complicated by valvular heart disease and associated with tissue fragility. The diagnosis of a type I collagen disorder was confirmed by abnormal COL1A1 or COL1A2 gene sequencing. One patient was investigated with electrophoresis of collagens from cultured skin fibroblasts, showing structurally abnormal collagen type I, skin biopsy showed unusual histology and abnormal collagen fibril ultra-structure at electron microscopy. The combined clinical, surgical, histological, ultra-structural, and molecular genetic data suggest the type I collagen defect as contributory to cardiac valvular disease. The degree of tissue fragility experienced at cardiac surgery in these individuals, also reported in a small number of similar case reports, suggests that patients with OI type I need careful pre-operative assessment and consideration of the risks and benefits of cardiac surgery.

  2. The Diagnosis Value of Ultrasound for Fetal Osteogenesis Imperfecta%超声对胎儿成骨发育不全的诊断价值

    Institute of Scientific and Technical Information of China (English)

    伍萍; 熊天波; 熊琳宁

    2012-01-01

    Objective:To investigate the diagnosis value of ultrasound examination for fetal osteogenesis imperfecta (OI). Method: Retrospectively analyzed the sonographic feature of 20 cases OI of pregnant women of fetal who were diagnosed by prenatal ultrasound and compared the results with X-ray or pathology determination after induction to assess the accuracy and value of ultrasound examination for fetal OI. Result: 17 cases of ultrasound examination results were confirmed to pathology results after induction, and the correct rate was 85 % , and all cases had the feature of short limbs and multiple fractures, including 9 cases had more amniotic fluid than the others. Conclusion: Prenatal ultrasound diagnosis may be more accurate to diagnose the skeletal abnormalities of the fetus, through the analysis of sonographic features and comparing with the X-ray or pathology results after induction, it shows that the results are basically consistent with them. It's importance significance for screening OI significance, and it is the preferred method for the prenatal diagnosis of fetal bone development.%目的:探讨超声检查对胎儿成骨发育不全(OI) 的诊断价值.方法:回顾总结我院自2006 年2 月至2011 年2 月经产前常规超声检查确诊为胎儿成骨发育不全的孕妇20 例的声像图特点,并将其与胎儿引产后由X 线或是病理证实的结果相比较,研究分析超声检查对胎儿成骨发育不全的诊断准确性及应用价值.结果:在本组20 例孕妇中,17 例超声检查与引产后的病理证实结果相符合,正确率达到85%.所有患儿均有四肢短小弯曲并多发骨折的特点,其中9 例胎儿羊水较多.结论:产前超声检查可较准确的诊断出胎儿骨骼发育异常,通过分析声像图特点并与引产后由X 线或病理证实的结果相对比,检测结果基本相符,对有效筛检OI 具有重要意义,有较好的临床价值,是对胎儿行产前诊断骨骼发育是否异常的首选方法.

  3. Fast Facts on Osteogenesis Imperfecta

    Science.gov (United States)

    ... often severe. Brittle teeth possible. Hearing loss possible. Collagen improperly formed. Type IV Between Type I and Type III in severity. ... do not have mutations in the type I collagen genes. Type V Clinically similar to Type IV in appearance and symptoms of OI. A dense ...

  4. 一成骨不全家系的COL1A1基因突变检测%Mutation Detection of COL1A1 Gene in a Pedigree with Osteogenesis Imperfecta

    Institute of Scientific and Technical Information of China (English)

    秦炜; 何隽祥; 施瑾; 邢清和; 高建军; 钱学庆; 刘壮俊; 舒安利; 贺林

    2005-01-01

    成骨不全(Osteogenesis imperfecta,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.%Osteogenesis imperfecta(OI)is heritable bone fragility,which is inherited as an autosomal dominant trait clinical presentation.Clinical symptom,in general,is dominantly inherited OI with blue sclerae,hearing loss and mild-moderate skeletal deformity.Genetic loci of OI have been mapped to17q21.31-q22 and 7q22.1,in which COL1A1 and COL1A2 are known to be the causal genes.In this work,we performed linkage analysis in a kindred with autosomal dominant hereditary OI.A tight linkage to the markers on chromosome 17q21.31-q22 (maximum two-point lod score:9.31 at θ=.00) was observed.Sequence analysis of COL1A1 revealed a single-base mutation that converted the consensus sequence at the 5′end of intron 26 from GT to AT to form an abnormal splicing site leading to OI.

  5. An overlapping phenotype of Osteogenesis imperfecta and Ehlers-Danlos syndrome due to a heterozygous mutation in COL1A1 and biallelic missense variants in TNXB identified by whole exome sequencing.

    Science.gov (United States)

    Mackenroth, Luisa; Fischer-Zirnsak, Björn; Egerer, Johannes; Hecht, Jochen; Kallinich, Tilmann; Stenzel, Werner; Spors, Birgit; von Moers, Arpad; Mundlos, Stefan; Kornak, Uwe; Gerhold, Kerstin; Horn, Denise

    2016-04-01

    Osteogenesis imperfecta (OI) and Ehlers-Danlos syndrome (EDS) are variable genetic disorders that overlap in different ways [Cole 1993; Grahame 1999]. Here, we describe a boy presenting with severe muscular hypotonia, multiple fractures, and joint hyperflexibility, features that are compatible with mild OI and hypermobility type EDS, respectively. By whole exome sequencing, we identified both a COL1A1 mutation (c.4006-1G > A) inherited from the patient's mildly affected mother and biallelic missense variants in TNXB (p.Val1213Ile, p.Gly2592Ser). Analysis of cDNA showed that the COL1A1 splice site mutation led to intron retention causing a frameshift (p.Phe1336Valfs*72). Type 1 collagen secretion by the patient's skin fibroblasts was reduced. Immunostaining of a muscle biopsy obtained from the patient revealed a clear reduction of tenascin-X in the extracellular matrix compared to a healthy control. These findings imply that the combination of the COL1A1 mutation with the TNXB variants might cause the patient's unique phenotype.

  6. Rehabilitation Nursing of 50 Patients with Osteogenesis Imperfecta Undergoing Femoral Orthtic Operation%成骨不全患儿股骨矫形术后康复护理

    Institute of Scientific and Technical Information of China (English)

    刘旭艳; 任秀智; 陈玉霞; 刘西芬; 房凤岭

    2015-01-01

    This paper summarized the rehabilitation nursing of 50 patients with osteogenesis imperfecta undergoing femoral orthtic operation. The postoperative rehabilitation consisted of 3 stages, including breathing exercise、muscle exercise、joint exercise、water therapy、walking period、free exercise period.Al 50 patients were cured and recovered without complications.Joint functions were recovered wel .%总结了50例成骨不全股骨矫形术后康复护理,术后分3个阶段实施康复训练,包括呼吸功能锻炼、肌肉功能锻炼、关节功能锻炼、水疗法、步行行走期、自由锻炼期。50例患儿术后无并发症发生,所有患儿术后关节活动范围正常,完全恢复正常生活。

  7. Asymptomatic parental mosaicism for osteogenesis imperfect associated with a new splice site mutation in COL1A2

    DEFF Research Database (Denmark)

    Frederiksen, Anja Lisbeth; Dunø, Morten; Johnsen, Iben Birgit Gade;

    2016-01-01

    Recurrent lethal perinatal osteogenesis imperfecta may result from asymptomatic parental mosaicism. A previously unreported mutation in COL1A2 leads to recurrent cases of fetal osteogenesis imperfecta Sillence type IIA, which emphasizes the importance of clinical and genetic evaluation of mosaicism...... in asymptomatic parents as verified mosaicism highly increases recurrence risk....

  8. Avaliação clínica, radiográfica e laboratorial de pacientes com osteogênese imperfeita Clinical, radiographic and laboratory evaluation of patients with osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Cláudio Santili

    2005-08-01

    Full Text Available OBJETIVOS: A osteogênese imperfeita (OI é uma doença genética, caracterizando-se por alterações no colágeno do tipo I, que determinam um espectro amplo de alterações clínicas, como a dentinogênese imperfeita e escleras azuladas. O objetivo deste estudo é estabelecer uma correlação prática no diagnóstico diferencial intergrupos dentro da classificação de Sillence et al. (1979. MÉTODOS: Foram avaliados 22 pacientes mediante critérios clínicos e radiográficos. Após, a subdivisão de acordo com os tipos de Sillence et al. (1979, os pacientes foram também submetidos à avaliação laboratorial e à densitometria óssea. RESULTADOS: Os dados significantes para diferenciação entre os tipos da doença foram a estatura, o número total de fraturas por indivíduo e a densitometria óssea. O cálcio sérico não diferencia os tipos da doença. CONCLUSÕES: Características como a deambulação, a estatura e a densitometria óssea podem auxiliar na diferenciação entre os subtipos dos portadores da doença, repercutindo diretamente no estabelecimento do seu prognóstico.BACKGROUND: Osteogenesis imperfecta is a genetic disorder characterized by defects in type I collagen. The main symptom is bone fragility and susceptibility to fractures. Other clinical findings are dentinogenesis imperfecta, blue sclera, early deafness and joint laxity. The purpose of this paper is to establish a practical relationship of the clinical differences between the Sillence's groups. METHODS: 22 patients were classified according to Sillence et al criteria and submitted to laboratory tests including blood calcium level and bone densitometry. RESULTS: All clinical and laboratory differences were discussed in the text. CONCLUSIONS: Differences such as results that were found in walking ability, height and bone densitometry were significant and may help to classify patients and to establish prognosis.

  9. Diagnostic conundrums in antenatal presentation of a skeletal dysplasia with description of a heterozygous C-propeptide mutation in COL1A1 associated with a severe presentation of osteogenesis imperfecta.

    Science.gov (United States)

    Marshall, Charlotte J; Arundel, Paul; Mushtaq, Talat; Offiah, Amaka C; Pollitt, Rebecca C; Bishop, Nicholas J; Balasubramanian, Meena

    2016-12-01

    Prompt and accurate diagnosis of skeletal dysplasias can play a crucial role in ensuring appropriate counseling and management (both antenatal and postnatal). When a skeletal dysplasia is detected during the antenatal period, especially early in the pregnancy, it can be associated with a poor prognosis. It is important to make a diagnosis in antenatal presentation of skeletal dysplasias to inform diagnosis, predict prognosis, provide accurate recurrence risks, and options for prenatal genetic testing in future pregnancies. Prenatal ultrasound scanning is a useful tool to detect several skeletal dysplasias and sonographic measurements serve as reliable indicators of lethality. The lethality depends on various factors including gestational age at which features are identified, size of the chest and progression of malformations. Although, it is important to type the skeletal presentation as accurately as possible, this is not always possible in an antenatal presentation and it is important to acknowledge this uncertainty. In the case of a live birth, it is always important to reassess the infant. Osteogenesis imperfecta (OI) is a heterogeneous group of disorders characterized by fragile bones. Here, we report an infant with severe OI born following a twin pregnancy in whom the bone disease is caused by a heterozygous pathogenic mutation, c.4160C >T, p.(Ala1387Val) located in the C-propeptide region of COL1A1. An assumption of lethality antenatally complicated his management in early life. We discuss this patient with particular emphasis on the neonatal presentation of a severe skeletal dysplasia and the lessons that may be learned in such situations. © 2016 Wiley Periodicals, Inc.

  10. G to A substitution in 5{prime} donor splice site of introns 18 and 48 of COL1A1 gene of type I collagen results in different splicing alternatives in osteogenesis imperfecta type I cell strains

    Energy Technology Data Exchange (ETDEWEB)

    Willing, M.; Deschenes, S. [Univ. of Iowa, Iowa City, IA (United States)

    1994-09-01

    We have identified a G to A substitution in the 5{prime} donor splice site of intron 18 of one COL1A1 allele in two unrelated families with osteogenesis imperfecta (OI) type I. A third OI type I family has a G to A substitution at the identical position in intron 48 of one COL1A1 allele. Both mutations abolish normal splicing and lead to reduced steady-state levels of mRNA from the mutant COL1A1 allele. The intron 18 mutation leads to both exon 18 skipping in the mRNA and to utilization of a single alternative splice site near the 3{prime} end of exon 18. The latter results in deletion of the last 8 nucleotides of exon 18 from the mRNA, a shift in the translational reading-frame, and the creation of a premature termination codon in exon 19. Of the potential alternative 5{prime} splice sites in exon 18 and intron 18, the one utilized has a surrounding nucleotide sequence which most closely resembles that of the natural splice site. Although a G to A mutation was detected at the identical position in intron 48 of one COL1A1 allele in another OI type I family, nine complex alternative splicing patterns were identified by sequence analysis of cDNA clones derived from fibroblast mRNA from this cell strain. All result in partial or complete skipping of exon 48, with in-frame deletions of portions of exons 47 and/or 49. The different patterns of RNA splicing were not explained by their sequence homology with naturally occuring 5{prime} splice sites, but rather by recombination between highly homologous exon sequences, suggesting that we may not have identified the major splicing alternative(s) in this cell strain. Both G to A mutations result in decreased production of type I collagen, the common biochemical correlate of OI type I.

  11. 成骨不全病人原代成骨细胞中胶原蛋白提取方法改良%Collagen extraction method for improvement of primary osteoblast cells in patients with osteogenesis imperfecta

    Institute of Scientific and Technical Information of China (English)

    张宇昂; 鲁艳芹; 任秀智; 刘军龙; 滕元伟; 韩金祥

    2016-01-01

    目的:本文对成骨不全患者骨骼中胶原蛋白的提取方法进行探讨,拟建立较为稳定的和可控的提取技术,为该病的治疗寻找新思路。方法:选取成骨不全患者在接受外科矫形手术中废弃的骨骼组织,经原代细胞培养后,采用盐析法配合胃蛋白酶消化提取细胞内和培养液中胶原蛋白。分别选取0.05~0.2mM抗坏血酸、0.1~0.25mMβ-氨基丙腈(BAPN)、0.5~1.5mg/mL胃蛋白酶进行梯度实验,比较胶原蛋白提取效果。抗坏血酸作用时间2到5天,每间隔24小时取样一次。胃蛋白酶作用时间,分别为5小时、10小时和20小时三个时间点进行比对。结果:从细胞中和培养液中提取的胶原蛋白,最适的胃蛋白酶消化时间为5小时,作用浓度1mg/mL。培养液中抗坏血酸浓度在0.1~0.15mM之间,β-氨基丙腈浓度达到0.1mM时,连续培养96h以上胶原蛋白产出量较高。结论:实验初步说明,通过优化后的胶原蛋白提取方法,可有效提取患者原代成骨细胞及细胞培养液中的胶原蛋白,有助于成骨不全相关研究的继续深入。%Objective:The paper aims to establish a stable and controllable method for collagen extraction from primary osteoblasts derived from osteogenesis imperfecta bone tissues.Methods:The primary osteoblasts were selected from the bone tissue of osteogenesis imperfecta patients who received deformity treatments. Collagen secreted from the cellular layer and culture medium was extracted by salting-out method and salting-out combined with pepsin digestion method, respectively. The different concentrations of L-ascorbate,ß-amino-propio-nitrille (BAPN) and pepsin were compared between 0.05~0.2mM, 0.1~0.25mM and 0.5~1.5mg/mL respectively. Different time points for L-ascorbate treatment were set at 2 days to 5 days, with an interval of 24 hours. For the pepsin digestion treatment, 5h, 10h and 20h time points were compared.Results: For the

  12. Genetic analysis in a family with Osteogenesis imperfecta type Ⅳ%Ⅳ型成骨发育不全家系的遗传分析

    Institute of Scientific and Technical Information of China (English)

    李松; 袁静; 许烨烨; 方慧琴; 丛林

    2015-01-01

    Objective:Clinical investigation analysis and genetic testing of a family with os—teogensis imperfecta typeⅣ,discussing the relationship between genotype and phenotype. Methods:Preliminary classification based on clinical characteristics of the family members,and then the appli—cation of high—throughput sequencing methods for rapid and accurate detection of changes in candi—date gene. Results:Genetic testing of the fetus ofⅢ5 and other members of the family revealed a missense mutation of c. 2746G>A,pGly916Arg in COL1A2 gene coding region and missense muta—tion,synonymous mutation in COL1A1 gene coding region. Conclusion:Clearing the relationship be—tween genotype and phenotype in a family with osteogensis imperfecta will provide fast,accurate ge—netic counseling and eugenics suggestions for OI patients and their families.%目的::对Ⅳ型成骨发育不全( OI )的一个家系进行临床调查分析和基因检测,探讨家族性成骨发育不全基因型与表型的关系。方法:根据临床特征对该家族成员进行初步分型,再采用高通量测序(high—throughput sequencing)的方法快速、准确地检测候选基因的变化。结果:Ⅲ5胎儿及家族内其他成员均存在COL1A2基因编码区多态性c.2746G〉A(p. Giy916Arg)和COL1A1基因编码区错义,同义突变。结论:明确家族性OI基因型与表型的关系将为OI患者及其家庭提供快速、准确地遗传咨询和优生建议。

  13. 多段截骨矫形髓内固定治疗儿童成骨不全症%Multi-section osteotomy and intramedullary fixation for children with osteogenesis imperfecta

    Institute of Scientific and Technical Information of China (English)

    任秀智; 曾裴; 李冰; 杨建平

    2012-01-01

    Objective To evaluate the safety,therapeutic effect and complications of the operation of multi-section osteotomy and intramedullary fixation for children with osteogenesis impeffecta.Methods One hundred and twenty-three children with osteogenesis imperfecta,including 85 males and 39 females,were selected from August 2005 to August 2008.According to the modified Sillence classification,45 cases was in type Ⅲ,74 in type Ⅳ,and 5 in type Ⅴ.Patients' age was ranging from 2 years and 1 month to 15 years and 7 months (mean,8 years and 3 months).The location of osteotomy was established according to the pre-operative measurement of X-ray image,and all the procedures of osteotomy were completed under direct vision.Then we chose the intramedullary pin with suitable size and insert the pin into femur from greater trochanter,and tibia from pelma.After the surgery,external fixation (spica cast for the femur,long leg plaster cast for the tibia) was made for further stabilization.Plaster supporters were removed 6 weeks later and all children began to stand and walk under the protection of orthoses.In addition,all patients received the treatment of pamidronate disodium periodically.Results All 123 children were followed up for an average of 38months (range,13-64 months).Parents of all children were satisfied with the result of surgical operation,and the children's self-care and motion ability improved obviously.Fourteen children were performed the second operation due to the translocation of Rush pin,and 25 children changed the internal fixation because of the shorter Rush pin 2 years postoperatively.Bone delayed union was not found in all patients.Conclusion Multi-section osteotomy and intramedullary fixation for children with osteogenesis imperfecta could correct skeletal deformity,improve motion ability and avoid second fracture efficiently.However,such complications as translocation of intramedullary pin and changing the internal fixation with the growth of child need

  14. Internal fixation in treatment of lower limb deformity caused by osteogenesis imperfecta in children%多段截骨矫形髓内固定治疗儿童成骨不全症致下肢畸形

    Institute of Scientific and Technical Information of China (English)

    任秀智; 吴国华; 曾裴; 杨建平

    2010-01-01

    成骨不全症(osteogenesis imperfecta)是一种基因异常而影响结缔组织合成的疾病.其中大多数类型是编码I型胶原的基因突变所致,其临床特征包括:骨骼脆性增加、骨质疏松、牙齿发育异常、蓝巩膜、关节松弛和脊柱侧弯.成骨不全症患儿因多次骨折、肢体畸形,严重干扰其负重行走功能,临床矫正畸形时面临骨质疏松、内固定容易松动;接骨板同定后因应力改变致接骨板两端易再骨折等问题.2005年8月至2007年12月,23例成骨不全症儿童(33处肢体)接受多段截骨矫形髓内同定治疗.股骨27处、胫腓骨6处.患儿手术时平均年龄8岁3个月(2岁1个月~15岁7个月).23例患儿均周期性静脉给予帕米膦酸二钠治疗.随访全部23例病例,平均随访时间2年2个月(1年1个月~3年4个月).全部患儿的父母对手术结果 及畸形矫正满意,生活自理能力、活动范围较术前有明显改善.接受帕米膦酸二钠治疗患儿截骨处未表现延迟愈合.

  15. Diagnóstico pré-natal e parto transpelviano na osteogênese imperfeita: relato de caso Prenatal diagnosis and vaginal delivery in osteogenesis imperfecta: a case report

    Directory of Open Access Journals (Sweden)

    Alex Sandro Rolland de Souza

    2006-04-01

    Full Text Available A osteogênese imperfeita é doença do tecido conjuntivo devida a anormalidades quantitativas ou qualitativas do colágeno tipo I, transmitida geneticamente, por gene autossômico dominante ou recessivo, que determina fragilidade óssea. Relata-se o caso clínico de paciente de 19 anos, primigesta, encaminhada ao setor de medicina fetal com ultra-sonografia pregressa evidenciando encurtamento de extremidades fetais. Na avaliação morfológica, identificou-se contorno craniano irregular com deformidade à compressão do pólo cefálico, membros com rizo e mesomelia, rarefação óssea e encurvamento de ossos longos (fraturas. A paciente evoluiu com parto transpelviano na 35ª semana de gestação. O recém-nascido apresentou Apgar de 6 no 1ª minuto e 8 no 5ª minuto, sexo masculino, pesando 1.990 gramas. Observado crânio irregular, ossificação diminuída, esclera azulada e fraturas consolidadas com deformidades em todos os membros. O recém-nascido apresentou boa evolução neonatal, recebendo alta hospitalar em boas condições. O diagnóstico pré-natal é de grande importância para adequado acompanhamento da gravidez e a via de parto transpelviana não ocasionou piora do prognóstico neonatal, pois não foram diagnosticadas fraturas recentes.Osteogenesis imperfecta is a connective tissue disorder due to quantitative and qualitative anomalies in type 1 collagen, genetically transmitted by a dominant or recessive autosomal gene, leading to bone fragility. We report a case of a 19-year-old G1 PO patient referred to our institution following a screening ultrasound that demonstrated short limb fetal extremities. A level 3 scan was performed which evidenced an irregular cranial shape and compression of the cephalic pole with moderate transducer pressure. Limb shortening, decreased echoes and fractures of long bones were found on our scan evaluation. A vaginal delivery occurred at 35 weeks of gestation. The male newborn, weighing 1.990 grams

  16. Long term complications of conservative treatment of lower leg fractures in children with osteogenesis imperfecta%成骨不全症儿童下肢骨折保守治疗的远期并发症

    Institute of Scientific and Technical Information of China (English)

    任秀智; 陈梅; 房凤岭; 刘军龙; 窦丛辉

    2015-01-01

    目的:分析成骨不全症儿童下肢骨折经保守治疗后的远期结果及其并发症。方法回顾性对比分析患者的系列 X 线片,2001年9月至2014年7月,我科共收治1100例成骨不全症患者,其中 Sillence 分型 I 型376例,III 型320例,IV 型404例。其中就诊时已经出现骨骺闭合者437例。其中既往反复下肢骨折均采用保守治疗(牵引、夹板或者石膏固定)且 X 线片资料完整者45例,男30例,女15例,就诊时平均年龄17(13~34)岁。Sillence 分型:I 型2例,III 型20例,IV 型23例。分析患者的骨折次数、每次骨折的肢体固定时间,记录最终随访时的下肢功能、下肢骨骼的形态变化以及最终随访时的 X 线片表现。结果45例每次骨折均采用保守治疗,骨折后肢体固定平均时间为50(30~90)天,多数骨折可愈合,但30例假关节形成,27例骨骺早闭。X 线片显示反复骨折需要长时间牵引或者石膏固定,患肢制动、不负重超过6个月以上者,X 线片显示骨质疏松异常加重。X 线片总体表现骨骼纤细、髓腔封闭、关节膨大、皮质变薄、骨骼多平面弯曲畸形。最终随访时5%的患者完全卧床,30%需要轮椅,35%可以拐杖辅助下短距离行走,30%可自行行走,部分伴有步态异常。30%的病例因为矫形和内固定困难已无法进行任何骨科治疗。结论成骨不全症儿童下肢骨折虽然经保守治疗可以愈合,但反复骨折和保守治疗后其远期功能结果和 X 线片表现差,应及时行截骨矫形髓内固定以尽早恢复肢体的负重功能,从而避免骨骼发育受阻。%Objective To analyze long term results and complications of conservative treatment for lower leg fractures in children with osteogenesis imperfecta.Methods The series X-ray iflm of 1100 patients admitted in our hospital from September 2001 to July 2014 were analyzed retrospectively. According to Sillence

  17. Screening and analysis of a new mutation of COL1A1 gene in a family with osteogenesis imperfecta%一个成骨不全家系COL1A1基因的突变筛查

    Institute of Scientific and Technical Information of China (English)

    白雪; 李克秋; 任秀智; 何晓波; 王毅; 官士珍; 景亚青; 李光

    2014-01-01

    Objective To investigate mutation of COL1A1 gene and analyze the relationship between genotype and clinical phenotype in a family with osteogenesis imperfecta (OI).Methods The family history of an OI pedigree,along with clinical data,was collected.Blood samples from the proband and his families,as well as 50 normal controls,were collected.Mutation of COL1A1 gene was screened using PCR-high resolution melting (PCR-HRM) and validated by sequencing.Results PCR-HRM method showed an abnormal result in proband COL1A1 33_34 exons,which Tm was 87.7℃,in contrast to the normal control (wt) Tm of 87.9 ℃ ± 0.06℃.There was a significant difference between the proband and the normal control with the standardization curve and the difference curves.DNA sequencing showed that COL1A1 gene exons 33_34 has lost a C base (c.2321delC),which resulted in a frameshift mutation and caused an premature termination codon (UAA) at amino acid 334,i.e.,p.Pro774LeufsX334.The father and grandfather of the proband,both suffered from OI,were verified to be heterozygous for the same mutation.The same mutation was not found in 50 normal controls.Database search confirmed this to be a novel mutation.Pedigree analysis suggested that it has an autosomal dominant inheritance.The proband and patients from the family were clinically diagnosed as OI type Ⅰ.Conclusion The study has identified a novel mutation of COL1A1 gene,c.2321delC.This frameshift mutation has caused a premature stop codon and reduced collagen type Ⅰ synthesis,characterized by a lighter OI clinical phenotype.%目的 筛查1个成骨不全(osteogenesis imperfecta,OI)家系中COL1A1基因的突变,并分析基因型与临床表型的关系.方法 收集先证者及家系成员临床资料,采集先证者、随诊家属及50名正常对照的外周血标本,应用PCR-高分辨率熔解曲线(high resolution melting,HRM)分析筛查COL1A1基因突变,基因测序确定突变位点.结果 PCR-HRM分析显示,先证者COL1A1

  18. Planning for Your Child's Surgery (Osteogenesis Imperfecta)

    Science.gov (United States)

    ... Blue Jeans for Better Bones Calendar Online Store Planning for Your Child's Surgery: What Parents Need to ... but the entire family as well. Before Surgery: Planning Become well informed. Taking care of your child ...

  19. Osteogenesis imperfecta%成骨不全

    Institute of Scientific and Technical Information of China (English)

    Nick Bishop; 付勇

    2006-01-01

    成骨不全(OI)有不同的分类方法。最常用的是经Glorieux改良的Sillence标准(表1)。按疾病的严重程度(轻、中、重)分类对治疗方法的采用(如二膦酸盐)有一定的指导作用。

  20. Amelogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    K P Mahesh

    2012-01-01

    Full Text Available Amelogenesis imperfecta (AI represents a group of developmental disorder of teeth structure, genomic in origin, which affects the structure and clinical appearance of enamel of all or nearly all the teeth, and which may be associated with morphologic or biochemical changes elsewhere in the body. It can be hypoplastic, hypomineralized, or both. Teeth affected may be discoloured, sensitive, or prone to disintegration. A case of yellow brown discoloration in a hindu female aged 26, reported with same chief complaint. On examination of the patient, generalized yellowish brown discoloration of the teeth was seen. Radiographic and histopathologic examination confirms the diagnosis of AI.

  1. PCR-HRM分析筛查成骨不全一家系患儿基因突变%PCR-HRM Analysis for Gene Mutation Screening in a Child with Osteogenesis Imperfecta

    Institute of Scientific and Technical Information of China (English)

    白雪; 李克秋; 任秀智; 何晓波; 王毅; 官士珍; 景亚青; 李光

    2014-01-01

    目的:采用PCR-高分辨率熔解曲线(HRM)分析筛查成骨不全(OI)一家系患儿(先证者)COL1A1基因突变位点,探讨其基因型与临床表型的联系。方法对先证者进行家族史及临床资料的调查,采集先证者、家属及50名正常对照者血液标本,应用PCR-HRM分析筛查先证者及正常对照者COL1A1基因突变,基因测序确证突变位点。结果先证者COL1A1基因17外显子筛查结果异常,其熔解温度(Tm)值比正常对照者Tm值低约0.4℃。先证者与正常对照者的标准熔解曲线及差异熔解曲线均有明显差异。测序结果为c.1138G>A,突变导致380位氨基酸由甘氨酸(Gly)变成丝氨酸(Ser):p.(Gly 380 Ser),为错义突变。先证者父亲、祖母均具有相同突变位点。先证者母亲及正常对照者基因测序结果无此突变。该突变在中国人群中未见报道。该家系遗传特征为常染色体显性遗传,先证者临床诊断为Ⅳ型OI,临床表型较严重。结论 PCR-HRM分析是有效的OI基因筛查新方法。COL1A1基因c.1138G>A突变在中国人群中为新发现的突变位点。α螺旋结构域Gly被替换可能导致较严重的临床表型。%Objective To investigate COL1A1 gene mutation by PCR-high resolution melting (PCR-HRM) and an-alyze the correlation between genotype and clinical phenotype in a child (proband) with osteogenesis imperfecta (OI). Methods The family history of OI pedigree along with the clinical data was collected. Blood samples from the proband and his family members, as well as 50 normal controls, were collected. The mutation of COL1A1 gene was screened using PCR-HRM and validated by the gene sequence. Results The detection of PCR-HRM showed the abnormal result of COL1A1 17 exon in proband with a lower melting temperature (Tm) value than that of normal controls by 0.4℃. There were signifi-cant differences in the standardization melting curve and the different

  2. COL1A1基因新的剪接突变c.3208G>A导致Ⅰ型成骨不全一家系%A novel splicing mutation in COL1A1 gene caused type Ⅰ osteogenesis imperfecta in a Chinese family

    Institute of Scientific and Technical Information of China (English)

    赵鼎; 杨俊梅; 郭振欣; 李瑞

    2014-01-01

    目的 探讨一个成骨不全家系中COL1A 1基因的突变.方法 收集一个成骨不全家系的临床资料,采用聚合酶链反应以及直接测序法对所有成员进行COL1A1基因突变的检测,同时在20名健康亲属以及200名非亲属对照中对发现的突变进行检测.结果 RNA剪接分析发现一个c.3208G>A突变,后者造成了一种新的剪接位点,从而导致移码突变.在患者的健康亲属及正常对照中未发现同样的突变.结论 COL1A1基因突变是导致成骨不全的主要原因之一,本研究结果进一步丰富了Ⅰ型胶原基因的突变谱.%Objective To study a family affected with osteogenesis imperfecta for potential mutations in COL1A1 gene.Methods Clinical data of an affected family was collected.Potential mutation of the COL1A1 gene was screened using polymerase chain reaction and direct sequencing.Suspected mutation was detected in 20 unaffected relatives and 200 unrelated healthy controls.Results Analysis of RNA splicing has revealed a c.3208G/A mutation,which created a new splice sites and led to a frameshift mutation.The same mutation was not detected in the unaffected relatives or the 200 healthy controls.Conclusion Mutations of the COL1A1 gene are one of the major causes of osteogenesis imperfecta in Chinese population.Our finding has enriched the mutation spectrum of type Ⅰ collagen genes.

  3. Genetic Aspects of Dentinogenesis Imperfecta

    Directory of Open Access Journals (Sweden)

    Elza Ibrahim Auerkari

    2015-10-01

    Full Text Available Dentinogenesis Imperfecta (DI is a hereditary, simple autosomal dominant disorder showing abnormalities in the dentin of the developing teeth and occurring at a rate of about 1 in 8000 births. The expression of DI shows a high penetrance and a low mutation rate. Two main types of DI appear to exist: type I which is the defect associated with osteogenesis imperfecta, and type II which is the classical hereditary opalescent dentin. The formerly proposed DI type III appears to be only a modified expression of the same gene as in the classical DI type II. Any gene therapy type of treatment is unrealistic for adolescent patients who already exhibit the symptoms. However, there is a good prospect for early screening since DI is inherited as a dominant disorder, and known trail from parents or siblings is a strong indication for later exposure to DI. At present there are no practical means to correct the genetic defect or to avoid the symptoms. Nevertheless, screening provides an early warning and helps to guide protective and restorative treatment so early that maximum amount of the natural dentition can be retained.

  4. Genetics Home Reference: amelogenesis imperfecta

    Science.gov (United States)

    ... Me Understand Genetics Home Health Conditions amelogenesis imperfecta amelogenesis imperfecta Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Amelogenesis imperfecta is a disorder of tooth development. This ...

  5. Substitutions of aspartic acid for glycine-220 and of arginine for glycine-664 in the triple helix of the pro alpha 1(I) chain of type I procollagen produce lethal osteogenesis imperfecta and disrupt the ability of collagen fibrils to incorporate crystalline hydroxyapatite.

    Science.gov (United States)

    Culbert, A A; Lowe, M P; Atkinson, M; Byers, P H; Wallis, G A; Kadler, K E

    1995-01-01

    We identified two infants with lethal (type II) osteogenesis imperfecta (OI) who were heterozygous for mutations in the COL1A1 gene that resulted in substitutions of aspartic acid for glycine at position 220 and arginine for glycine at position 664 in the product of one COL1A1 allele in each individual. In normal age- and site-matched bone, approximately 70% (by number) of the collagen fibrils were encrusted with plate-like crystallites of hydroxyapatite. In contrast, approximately 5% (by number) of the collagen fibrils in the probands' bone contained crystallites. In contrast with normal bone, the c-axes of hydroxyapatite crystallites were sometimes poorly aligned with the long axis of fibrils obtained from OI bone. Chemical analysis showed that the OI samples contained normal amounts of calcium. The probands' bone samples contained type I collagen, overmodified type I collagen and elevated levels of type III and V collagens. On the basis of biochemical and morphological data, the fibrils in the OI samples were co-polymers of normal and mutant collagen. The results are consistent with a model of fibril mineralization in which the presence of abnormal type I collagen prevents normal collagen in the same fibril from incorporating hydroxyapatite crystallites. Images Figure 1 Figure 2 Figure 3 PMID:7487936

  6. Amelogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Aldred Michael

    2007-04-01

    Full Text Available Abstract Amelogenesis imperfecta (AI represents a group of developmental conditions, genomic in origin, which affect the structure and clinical appearance of enamel of all or nearly all the teeth in a more or less equal manner, and which may be associated with morphologic or biochemical changes elsewhere in the body. The prevalence varies from 1:700 to 1:14,000, according to the populations studied. The enamel may be hypoplastic, hypomineralised or both and teeth affected may be discoloured, sensitive or prone to disintegration. AI exists in isolation or associated with other abnormalities in syndromes. It may show autosomal dominant, autosomal recessive, sex-linked and sporadic inheritance patterns. In families with an X-linked form it has been shown that the disorder may result from mutations in the amelogenin gene, AMELX. The enamelin gene, ENAM, is implicated in the pathogenesis of the dominant forms of AI. Autosomal recessive AI has been reported in families with known consanguinity. Diagnosis is based on the family history, pedigree plotting and meticulous clinical observation. Genetic diagnosis is presently only a research tool. The condition presents problems of socialisation, function and discomfort but may be managed by early vigorous intervention, both preventively and restoratively, with treatment continued throughout childhood and into adult life. In infancy, the primary dentition may be protected by the use of preformed metal crowns on posterior teeth. The longer-term care involves either crowns or, more frequently these days, adhesive, plastic restorations.

  7. Mutation analysis and prenatal diagnosis of COL1A1 gene in a Chinese family with type Ⅰ osteogenesis imperfecta%一个Ⅰ型成骨不全家系COL1A1基因的剪切位点新突变及产前诊断

    Institute of Scientific and Technical Information of China (English)

    张卉; 吴东; 侯巧芳; 刘治佑; 秦利涛; 廖世秀

    2014-01-01

    Objective To detect mutation of COL1A1 gene in a Chinese family affected with type Ⅰ osteogenesis imperfecta (OI) and to provide prenatal diagnosis for a fetus at 17th gestational week.Methods Polymerase chain reaction,DNA sequencing and restriction endonuclease analysis were used to verify the detected mutation among other members of the family and 100 healthy controls.Results No mutation has been detected in the COL1A2 gene in all of the subjects.A heterozygous mutation c.104-1G>C was identified in the COL1A1 gene among all patients from this family.The same mutation was not found in other members from the family and the 100 healthy controls.The mutation was not found in the fetus,and was verified to be a new mutation according to the type Ⅰ collagen mutation database.Conclusion The c.104-1G>C mutation of the COL1A1 gene probably underlies the type Ⅰ osteogenesis imperfecta in this family.Under the premise of a clear genetic diagnosis,prenatal diagnosis may be provided to reduce the risk for the disease.%目的 确定1个汉族成骨不全家系COL1 A1基因的突变情况,为家系胎儿提供产前诊断.方法 应用测序方法对家系成员及100名正常对照者的COL1A1和COL1A2基因进行突变检测.结果 基因测序结果显示先证者及家系中7例存活患者的COL1A1基因的剪接位点存在c.104-1G>C突变,但是在正常家系成员以及100名无亲缘关系的正常对照中均未检测到该突变.经查询Ⅰ型胶原突变数据库该突变为未报道过的新突变.该家系所有成员COL1A2基因未检测到突变.胎儿的COL1A1基因测序结果正常,随访时的基因突变检测结果与产前诊断结果一致.结论 COL1A1基因c.104-1G>C突变是该家系的致病原因,在明确致病突变基因的前提下可对家系胎儿进行产前诊断,以避免成骨不全患儿的出生.

  8. A hospitalização e o adoecimento pela perspectiva de crianças e jovens portadores de fibrose cística e osteogênese imperfeita The hospitalization and the process of becoming ill through the children's and adolescents' perspective with cystic fibrosis and osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Daniele Borges de Mello

    2010-03-01

    Full Text Available O presente artigo visa discutir os resultados de uma pesquisa realizada em um hospital localizado no município do Rio de Janeiro, considerado referência em saúde da criança, do adolescente e da mulher. Analisamos os significados da hospitalização e do adoecimento crônico na infância e adolescência pela perspectiva de crianças e adolescentes com fibrose cística e osteogênese imperfeita durante suas internações hospitalares com vistas a explorar suas vivências e suas possibilidades de expressão enquanto sujeitos de conhecimento. Para tanto, privilegiamos a observação e a construção de suas produções mediadas pelo suporte lúdico, utilizando o desenho e/ou história como relevantes vias de acesso aos conteúdos infanto-juvenis. Os dados advindos desse estudo apontam para a capacidade de aquisição e produção de conhecimento que crianças e jovens possuem acerca de sua situação de adoecimento.The present article intends to discuss the results of a study completed in a hospital located in the municipal district of Rio de Janeiro, considered most prominent for child, adolescent and woman's health. We analyzed the meanings of hospitalization and chronic illness in childhood and adolescence through the perspective of children and adolescents with cystic fibrosis and osteogenesis imperfecta during their hospitalizations in order to explore their experience and communicative possibilities as knowledgeable informants. Hence, we privileged the observation and the construction of their productions through games, using drawings and/or story-telling as a relevant approach to childhood and adolescence contents. The data collected signify the acquisition and knowledge production capacity of children and adolescents concerning their illness processes.

  9. 新生儿成骨不全Ⅱ型的尸检和MSCT鉴定1例(英文)%Determination of a Newborn with Lethal Type H Osteogenesis Imperfecta and Other Anomalies Using Autopsy and Postmortem MSCT——A Case Report

    Institute of Scientific and Technical Information of China (English)

    邹冬华; 邵煜; 张建华; 万雷; 秦志强; 刘宁国; 黄平; 陈忆九

    2016-01-01

    本文报道了1例成骨不全(osteogenesis imperfecta,OI)Ⅱ型死胎案例.在妊娠期间胎儿即有颅骨骨折和颅脑损伤.法医尸体检验后,随即进行尸体多层螺旋CT(multi-sliced computed tomography,MSCT)扫描和三维重建.尸检结果显示了OIⅡ型的典型特征,包括颅骨变软、四肢畸形、髋关节弯曲和外展及一些异常特征如白色巩膜、髋内翻、部分骨骼和器官缺失、唇裂和两耳不对称.CT检测到的异常变化有腭裂、下颌发育异常、脊柱裂、颈肋、肋骨和椎骨融合,这些都是在常规尸检中难以检测到的.本文阐述了OI的分类、致病性基因突变、死亡原因以及OI与儿童受虐的鉴别,更强调了OI学科知识对法医病理学工作者的重要性和MSCT在法医病理学尸体检验中的价值.

  10. [Distraction osteogenesis in orthopaedics

    NARCIS (Netherlands)

    Baat, P. de; Baat, C. de; Bessems, J.H.

    2008-01-01

    For several decades, distraction osteogenesis has been applied in orthopaedics for lengthening limbs. Other indications for distraction osteogenesis in orthopaedics are nonunions, open fractures, oncologic defects, and ankle osteoarthritis. The main principle of distraction osteogenesis is that, wit

  11. Distraction osteogenesis.

    Science.gov (United States)

    Sidman, James; Tatum, Sherard Austin

    2014-02-01

    James Sidman, MD, and Sherard A. Tatum, MD, address the following questions for discussion and debate. Is neonatal distraction osteogenesis (DO) better than lip-tongue adhesion or tracheotomy for micrognathic airway compromise? What role does DO have in adult orthognathic surgery situations? In monobloc and Le Fort III procedures, are internal or external devices preferable? What role does DO play in craniofacial microsomia? Is endoscopic DO better than open procedures for synostosis management? How has your technique changed or evolved over the past 5 years and what has doing this technique taught you?

  12. Identification of a novel splicing mutation in COL1A1 gene in a Chinese family affected with type Ⅰ osteogenesis imperfecta%COL1A1基因中一个导致Ⅰ型成骨不全的新剪接突变c.3208G>A分析

    Institute of Scientific and Technical Information of China (English)

    宋银森; 金湘东; 孔京慧; 赵鼎; 郭振欣

    2014-01-01

    目的 探讨COL1A1基因中一个新突变c.3208G>A导致Ⅰ型成骨不全的致病机理.方法 应用标准的方法提取外周血全基因组DNA,PCR扩增基因的整个编码区域和内含子-外显子边界,应用ABI 3100/3130测序仪对PCR产物进行直接测序.从患者的EB病毒转化永生B细胞系中提取全RNA,用寡(dT) 18引物合成第一链cDNA,对PCR产物直接测序或者用TA克隆质粒DNA测序.结果 在一个Ⅰ型成骨不全大家庭中检测到一种位于COL1A1基因上的新突变c.3208G>A,为剪接突变.结论 发现了COL1A1基因中的新的剪接突变c.3208G>A.%Objective To investigate the genetic cause for a large family affected with type Ⅰ osteogenesis imperfecta.Methods Genomic DNA was extracted from peripheral venous blood samples.The entire coding region and intron-exon boundaries of the COL1A1 gene were subjected to PCR amplification and direct sequencing.Total RNA was also extracted from immortalized B cell lines from the patients,with the first strand of cDNA synthesized with an oligo(dT)18 primer.The PCR products were directly sequenced using the TA cloned plasmid.Results A c.3208G> A mutation has been identified in the COL1A1 gene,which can alter the splicing pattern of mRNA.Conclusion A novel splicing mutation c.3208G>A of the COL1A1 gene probably underlies the disease.

  13. Analysis of type Ⅳ osteogenesis imperfecta caused by two mutations occurred simultaneously in COL1A1 gene in a Chinese child%成骨不全患儿COL1A1基因第45外显子两个突变位点的筛查及分析

    Institute of Scientific and Technical Information of China (English)

    鞠明艳; 张天可; 白雪; 任秀智; 李克秋; 李光

    2016-01-01

    目的 应用聚合酶链反应-高分辨率熔解曲线分析(polymease chain reaction-high-resolution melting analysis,PCR-HRMA)技术筛查成骨不全症(osteogenesis imperfecta,OI)患者COL1A1/COL1 A2基因的突变,并探讨突变位点与疾病的关系.方法 采集家系成员(患儿、患儿父母)以及50名正常对照的血液样本,应用PCR-HRMA技术筛查患儿家系及正常对照者的COL1A1/COL1A2基因突变,并用基因测序验证.应用蛋白预测软件PolyPhen、SIFT及Align GVGD对两个杂合突变进行预测.结果 该患儿及其父母COL1A1基因第45外显子区域的PCR-HRMA结果显示异常,标准熔解曲线和差异熔解曲线与正常对照比较均存在明显差异.测序结果显示,患儿COL1A1基因第45外显子区域发生两个杂合突变(c.3235G>A、c.3247G>A),临床诊断为Ⅳ型OI.c.3235G>A来源于患有OI的父亲,使α螺旋结构域1079位氨基酸由甘氨酸(Gly)突变为丝氨酸(Ser).c.3247G>A来源于表型正常的母亲,使1083位氨基酸由丙氨酸(Ala)突变为苏氨酸(Thr).50名正常对照均未发现这两种突变.3种蛋白预测软件PolyPhen、SIFT及Align GVGD均预测c.3235G>A突变可能影响蛋白的功能.而c.3247G>A突变,PolyPhen软件预测其可能为良性.结论 COL1A1基因第45外显子上同时存在c.3235G>A、c.3247G>A突变的病例在人类胶原突变数据库中未见报道.COL1A1基因c.3235G>A突变可能是导致该患儿成骨不全的主要原因.%Objective To detect potential mutations of COL1A1 and COL1A2 genes with polymerase chain reaction-high-resolution melting analysis (PCR-HRMA) in a proband diagnosed with osteogenesis imperfecta (OI).Methods Peripheral blood samples were collected from the proband and members of his family as well as healthy controls.The mutations were detected by PCR-HRMA and confirmed by direct sequencing.Potential effects of the mutations were predicted using softwares including PolyPhen,SIFT and Align GVGD

  14. Genetic screening of a pedigree with osteogenesis imperfecta type Ⅰand identification of a novel mutation in COL1A2 pathogenic gene%成骨不全Ⅰ型家系的基因检测和COL1A2基因新突变的致病性鉴定

    Institute of Scientific and Technical Information of China (English)

    李荣; 郭源平; 潘敬新; 郭奕斌

    2015-01-01

    To uncover the molecular pathogenic mechanism of congenital osteogenesis imperfecta (OI) type I, all the 103 exons of the COL1A1 (Collagen, type Ⅰ, alpha 1) and COL1A2 (Collagen, type Ⅰ, alpha 2) genes in a child with OI type Ⅰ were screened using PCR-DNA direct sequencing. The results showed no pathological mutation in COL1A1 gene, but a novel mutation c.946G>T/p.G316C in the exon 19 of COL1A2 gene, which was inherited from her father. This mutation was not found in her mother and other six phenotypically normal relatives. By denaturing high perfor-mance liquid chromatography (DHPLC) screening, the abnormal double-peak was visualized in PCR products of exon 19 of COL1A2 gene in the proband and her father, while the normal single-peak was shown in those of her mother and all the healthy controls. Using allele specific amplification (ASA) screening, a specific band of 391 bp in COL1A2 exon 19 was amplified only in the proband and her father, but not in other samples. The amino acid encoded by the mutation site is evolutionarily highly conserved, and this mutation was a“damaging”or“probably damaging”factor to OI type Ⅰ, based on the predicting results using SIFT and Polyphen-2 softwares. In conclusion, the novel c.946G>T/p.G316C mutation in COL1A2 gene is a pathogenic mutation that could result in OI type Ⅰ. If the couple wants to get pregnant again, it is necessary to screen the mutation site in COL1A2 gene through the prenatal genetic diagnosis in the first trimester or through preimplantation genetic diagnosis (PGD) in the progestation.%为了揭示成骨不全(Osteogenesis imperfecta, OI)Ⅰ型家系的分子遗传学发生机制,文章采用PCR-DNA直接测序法,对患儿 COL1A1和 COL1A2基因共103个外显子(E)进行突变检测。结果显示:患儿 COL1A1基因未发现任何病理性突变,而在 COL1A2基因 E19内发现一新的杂合错义突变(p.G316C),该突变来自其父,而其母正常,其他表型正常的6位

  15. Use of minimally invasive operation therapy with extended intramedullary nail on children with femoral fracture and deformity due to osteogenesis imperfecta%可延长髓内钉微创治疗成骨不全术后股骨再发畸形或骨折

    Institute of Scientific and Technical Information of China (English)

    房凤岭; 任秀智; 冯世庆; 李志良; 王风君; 袁桐强

    2013-01-01

    目的 探讨可延长髓内钉治疗成骨不全术后股骨再发畸形或骨折的疗效.方法 回顾性分析2009年6月至2012年6月采用可延长髓内钉治疗21例成骨不全术后股骨再发畸形或骨折患儿资料,男13例,女8例;年龄9岁6个月至15岁7个月,平均12岁3个月.所有患儿均已行股骨干截骨矫形不可延长髓内钉手术,此次手术距初次手术时间为2~4年,平均3年.所有患儿成长肢体于髓内钉远端部位再次出现畸形或骨折,其中9例为股骨干弯曲畸形,畸形成角度数为10°~30°,平均15°;12例为再发骨折.依据修订后的Sillence分型:Ⅲ型6例,Ⅳ型14例,Ⅴ型1例.21例患儿均在大转子及远端截骨处切开手术,切口长度为2~3 cm,采用可延长髓内钉再次固定骨折及矫正畸形.结果 21例患儿均获得随访,随访时间6~30个月,平均18个月.骨折愈合时间为7~12周,平均8.5周.待X线片示截骨愈合后患儿开始负重行走.所有患儿及其父母均对手术结果及畸形矫正效果表示满意,末次随访时患儿Barthel指数评分由术前平均72.85分(范围,50~90分)提高到术后平均91.42分(范围,80~100分).WeeFIM评分由术前平均55.42分(范围,40~70分)提高到术后平均79.00分(范围,70~86分).10例术前需拐杖辅助行走患儿,随访时可独立行走;6例术前因骨折而卧床患儿中,4例可独立行走,2例需拄拐活动.末次随访时,无一例出现感染、骨髓炎等并发症,无神经、血管损伤病例.结论 应用可延长髓内钉小切口手术,对肢体损伤小、出血少、骨折愈合时间短、患儿痛苦小,是治疗成骨不全术后股骨再发畸形或骨折的良好方法.%Objective To evaluate the therapeutic effect of extendable intramedullary nail on children with femoral deformity due to osteogenesis imperfecta.Methods From June 2009 to June 2012,21 patients with femoral deformity due to osteogenesis imperfecta were treated with extendable

  16. Dentinogenesis imperfecta associated with short stature, hearing loss and mental retardation: a new syndrome with autosomal recessive inheritance?

    Science.gov (United States)

    Cauwels, R G E C; De Coster, P J; Mortier, G R; Marks, L A M; Martens, L C

    2005-08-01

    The follow-up history and oral findings in two brothers from consanguineous parents suggest that the association of dentinogenesis imperfecta (DI), delayed tooth eruption, mild mental retardation, proportionate short stature, sensorineural hearing loss and dysmorphic facies may represent a new syndrome with autosomal recessive inheritance. Histological examination of the dentin matrix of a permanent molar from one of the siblings reveals morphological similarities with defective dentinogenesis as presenting in patients affected with Osteogenesis Imperfecta (OI), a condition caused by deficiency of type I collagen. A number of radiographic and histological characteristics, however, are inconsistent with classical features of DI. These findings suggest that DI may imply greater genetical heterogeneity than currently assumed.

  17. Prosthodontic rehabilitation of dentinogenesis imperfecta

    OpenAIRE

    2011-01-01

    Dentinogenesis imperfecta and its prosthodontic management is a challenging task. Treatment protocol varies according to clinical case. Although various reports in the literature suggest general guidelines for treatment planning, the present case report describes a full mouth rehabilitation of a young patient with dentinogenesis imperfecta treated by maxillary fixed partial dentures and mandibular fiber reinforced overdenture with metal occlusal surfaces.

  18. Prosthodontic rehabilitation of dentinogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Anil Goud

    2011-01-01

    Full Text Available Dentinogenesis imperfecta and its prosthodontic management is a challenging task. Treatment protocol varies according to clinical case. Although various reports in the literature suggest general guidelines for treatment planning, the present case report describes a full mouth rehabilitation of a young patient with dentinogenesis imperfecta treated by maxillary fixed partial dentures and mandibular fiber reinforced overdenture with metal occlusal surfaces.

  19. Prosthodontic rehabilitation of dentinogenesis imperfecta.

    Science.gov (United States)

    Goud, Anil; Deshpande, Saee

    2011-04-01

    Dentinogenesis imperfecta and its prosthodontic management is a challenging task. Treatment protocol varies according to clinical case. Although various reports in the literature suggest general guidelines for treatment planning, the present case report describes a full mouth rehabilitation of a young patient with dentinogenesis imperfecta treated by maxillary fixed partial dentures and mandibular fiber reinforced overdenture with metal occlusal surfaces.

  20. Fracture Rates and Fracture Sites in Patients With Osteogenesis Imperfecta

    DEFF Research Database (Denmark)

    Folkestad, Lars; Hald, Jannie Dahl; Ersbøll, Annette Kjaer;

    2016-01-01

    , with a peak during the toddler and adolescent years (incidence rate [IR] 233.9 per 1000 person years), fewer fractures during adulthood (IR 84.5 per 1000 person years), and increased fracture rates in older women (IR 111.9 per 1000 person years). This is the largest register-based nationwide study...... years. In comparison, 709 persons in the reference population experienced a total of 1018 fractures during follow-up. Both male and female patients with OI had an increased fracture rate throughout their life. The fracture rate ratio for participants aged 0 to 19 years was 10.7, for participants aged 20...... to 54 years 17.2, and for participants aged 55 years and over 4.1 when compared to the reference population. The highest fracture rate was seen in males with OI aged 0 to 19 years (257 fractures per 1000 person-years). The fractures appear to follow the same pattern as in the general population...

  1. Forstørret nakkefold kan ses ved osteogenesis imperfecta

    DEFF Research Database (Denmark)

    Schönewolf-Greulich, Bitten; Skibsted, Lillian; Maroun, Lisa Leth;

    2011-01-01

    . In the present case, ultrasound scanning at 13 weeks of gestation showed a NT of 3.2 mm and no other pathological findings. At 20 weeks a severe skeletal dysplasia was diagnosed by ultrasound. The pathology report of the aborted foetus indicated OI, and DNA analysis confirmed a COL1A1 mutation....

  2. How Do Health Care Providers Diagnose Osteogenesis Imperfecta?

    Science.gov (United States)

    ... ee-on-ik VILL-uhs ) sampling (CVS) or amniocentesis (pronounced am-nee-oh-sen-TEE-sis ). The ... tested for the presence of abnormal collagen. For amniocentesis, a health care provider takes a small amount ...

  3. Amelogenesis imperfecta: an introduction.

    Science.gov (United States)

    Gadhia, K; McDonald, S; Arkutu, N; Malik, K

    2012-04-27

    Amelogenesis imperfecta (AI) is an inherited disorder that is associated with mutations in five genes (AMEL; ENAM; MMP20; KLK4 and FAM83H) with a wide range of clinical presentations (phenotypes). It affects the structure and appearance of enamel of all teeth, both in the primary and secondary dentition. In this review paper, we look at the epidemiology, classification, aetiology, clinical description and diagnosis of AI. In the following three papers of this series, we aim to describe the role of paediatric dentists, orthodontists and restorative dentists in the clinical management of patients with AI.

  4. 成骨不全症患者COL1A1/2致病突变谱和基因诊断研究%Spectrum of COL1A1/2 mutations and gene diagnosis in Chinese patients with osteogenesis imperfecta

    Institute of Scientific and Technical Information of China (English)

    赵秀丽; 肖继芳; 汪涵; 任秀智; 高劲松; 吴易阳; 卢超霞; 张学

    2015-01-01

    目的 在成骨不全症(OI)患者中鉴定Ⅰ型胶原基因(COL1A1和COL1A2)致病突变,构建中国人OI致病基因突变谱,并在此基础上完成OI高危胎儿的产前基因诊断.方法 应用酚/氯仿法提取先证者及家系成员外周血基因组DNA,联合应用聚合酶链反应(PCR)-Sanger DNA测序和靶向高通量测序技术对200例OI先证者进行COL1A1/2编码区及外显子/内含子衔接区的DNA序列分析;采用PCR-高分辨熔解曲线(HRM)技术对先证者及其家系成员进行突变验证;通过PCR-测序对散发病例的父母样本进行突变检测,进而确定突变来源;联合应用PCR-测序和微卫星标记等位基因分析的方法进行胎儿产前基因诊断.结果 在158例先证者中,发现COL1A1/2基因致病突变125种,包含COL1A1突变74种(91例),COL1A2突变51种(67例),阳性检出率79% (158/200);发现新突变63种,包括33种COL1A1突变和30种COL1A2突变.在上述125种COL1A1/2基因突变中,13种突变分别在2例以上先证者中重复出现(其中6种突变重复出现4次以上),合计检出46次,检出率为29.11% (46/158);完成产前基因诊断74例,其中包括患儿40例,正常胎儿34例.结论 建立基于Sanger DNA测序、靶向高通量测序和PCR-高分辨熔解曲线分析技术的OI基因诊断平台.在中国人群中,构建了OI相关COL1A1/2基因致病突变谱,并在此基础上完成大样本OI患者和高危胎儿的基因诊断.%Objective To identify mutations of the type Ⅰ collagen genes (COL1A1 and COL1A2) in the affected with osteogenesis imperfecta (OI) , to establish the spectrum of COL1A1/2 mutations in Chinese OI patients, and to provide prenatal gene diagnosis to the fetuses at high risk.Methods Genomic DNA was extracted from peripheral blood by the standard SDS-proteinase K-phenol/chloroform method.All the coding regions and exon/intron boundaries of COL1A1/2 were screened in 200 OI cases by conventional Sanger sequencing and targeted next

  5. COL1A1/COL1A2基因突变分析与成骨不全的产前基因诊断%Gene mutation analysis of COL1A1/COL1A2 and prenatal genetic diagnosis of osteogenesis imperfecta

    Institute of Scientific and Technical Information of China (English)

    李焕铮; 唐少华; 毛义建; 谢丙乐

    2012-01-01

    Objective: In this study, the patients with OI pregnancy history were required to have ultrasound ( US) examination and COL1A1/COL1A2 gene mutation detection. It is helpful to establish a clinical protocol for OI patient and provide the technical security for prenatal diagnosis. Methods: The pregnant woman with Oi pregnancy history must be monitored by US. According to ultra-sonography of fetal femur and long bone, it was diagnosed as OI. Amniotic fluid was drawn from pregnant woman with ultrasound abnormality. The sample was detected for COL1A1 and C0L1A2 mutations using direct sequencing. According to the result of new mutation detection, the COL1A1 and C0L1A2 genetic mutation for all family members were detected and analyzed. Identification of maternal blood contamination must be done before tests. Results; The ultrasound imaging showed that the fetus' femur was short, tibiofibula was angled bend, skull was thinning and multiple fractures were found. So we consider fetus was OI. The sample was identified without maternal blood contamination by STR. The COL1A1 of fetus was identified with 19 SNP loci, but no mutation was found. The C0L1A2 was identified with 13 SNP loci, and a G and A heterozygosis mutation at the exon 36 was found. The pregnant woman was found with the same mutation, but the clinical picture was different. Other members were tested with no detectable mutation. Conclusion; The pregnant woman with OI pregnancy history would be monitored by US and detected by genetic tests. It is very import for the sake of birth defects prevention.%目的 对有成骨不全(Osteogenesis Imperfecta,OI)孕史的患者,进行系统B超及COLtA1/COL1A2基因检测,希望建立OI患儿产前诊断方案,为OI患儿进行产前诊断提供技术保障.方法 对于有OI孕史的孕妇,进行系统B超监测;根据胎儿股骨、长骨的超声影像学表现,初诊为成骨不全.抽取羊水,采用直接测序法对羊水DNA的COL1A1和COL1A2基因全编码外显子

  6. Amelogenesis imperfecta: a clinician's challenge.

    Science.gov (United States)

    Chamarthi, V; Varma, B R; Jayanthi, M

    2012-01-01

    Defective enamel formation can be explained as defects occurring at the stages of enamel formation. Quantitative defects in matrix formation leads to hypoplastic form of amelogenesis imperfecta. Inadequate mineralization of matrix leads to hypocalcification and hypomaturation variants. The demarcation of matrix formation and mineralization is not so distinct. This paper describes a case of a 7-year-old boy with amelogenesis imperfecta - Type IA i.e., hypoplastic pitted autosomal dominant.

  7. Osteogénesis imperfecta con manifestaciones en el periodo neonatal Neonatal Presentation of Osteogenesis Imperfecta

    OpenAIRE

    Gilberto Rodríguez-Herrera; María Jesús Navarro-Charpantier

    2009-01-01

    Se reporta un caso de un paciente masculino de un día de vida extrauterina; producto de una madre de 20 años, primigesta, prima segunda de su pareja. Nace por cesárea por presentación pélvica, con líquido amniótico meconizado, con un peso al nacer de 2275 gramos (RNTPEG). Al examen físico el niño se encontraba flácido, con cianosis leve, fontanelas amplias con comunicación de la anterior con la posterior, ausencia de escama occipital, escleras azules, retrognatia, extremidades cortas y con cr...

  8. Dentinogenesis imperfecta type I: A case report with literature review on nomenclature system

    Directory of Open Access Journals (Sweden)

    D Devaraju

    2014-01-01

    Full Text Available Dentinogenesis imperfecta (DI is an inherited disorder affecting dentin. Defective dentin formation results in discolored teeth that are prone to attrition and fracture. Mutation in dentin sialophosphoprotein (DSPP has been found to cause the dentin disorders DI - I and II (shields II and III. Early diagnosis and treatment of DI is recommended as it may prevent or intercept deterioration of the teeth and occlusion and improve esthetics. Here, we report a case with characteristic clinical, radiological and histological features of DI-I. The etiology and classification followed in literature is confusing since dentinoenamel junction (DEJ in DI seems to be structurally and functionally normal and DI is clearly a disorder distinct from osteogenesis imperfecta (OI, but we still relate etiology of DI to DEJ and follow Shields classification. Therefore, we have briefly reviewed etiology and nomenclature system of DI.

  9. Dentinogenesis imperfecta type I: A case report with literature review on nomenclature system.

    Science.gov (United States)

    Devaraju, D; Devi, Bk Yashoda; Vasudevan, Vijeev; Manjunath, V

    2014-09-01

    Dentinogenesis imperfecta (DI) is an inherited disorder affecting dentin. Defective dentin formation results in discolored teeth that are prone to attrition and fracture. Mutation in dentin sialophosphoprotein (DSPP) has been found to cause the dentin disorders DI - I and II (shields II and III). Early diagnosis and treatment of DI is recommended as it may prevent or intercept deterioration of the teeth and occlusion and improve esthetics. Here, we report a case with characteristic clinical, radiological and histological features of DI-I. The etiology and classification followed in literature is confusing since dentinoenamel junction (DEJ) in DI seems to be structurally and functionally normal and DI is clearly a disorder distinct from osteogenesis imperfecta (OI), but we still relate etiology of DI to DEJ and follow Shields classification. Therefore, we have briefly reviewed etiology and nomenclature system of DI.

  10. Esthetic reconstruction of teeth in patient with dentinogenesis imperfecta--a case report.

    Science.gov (United States)

    Knezević, Alena; Tarle, Zrinka; Pandurić, Vlatko

    2006-03-01

    Dentinogenesis imperfecta (DI) is the result of a dominant genetic defect and affects both the deciduous and permanent dentitions. It is characterized by opalescent teeth composed of irregularly formed and undemineralized dentin which obliterates pulp chamber and root canal. DI can appear as a separate disorder or with osteogenesis imperfecta (OI). The teeth with DI show a grayish-blue to brown hue with dislodged enamel, dysplastic dentine with irregular dentinal tubules and interglobular dentine, short roots and pulpal obliteration, which all may lead to rapid and extensive attrition which require adequate crown reconstruction. The aim of this study was to show a reconstruction of frontal teeth in upper jaw with direct composite veneers in young adult patient with DI.

  11. Amelogenesis imperfecta: the orthodontic perspective.

    Science.gov (United States)

    Arkutu, N; Gadhia, K; McDonald, S; Malik, K; Currie, L

    2012-05-25

    Orthodontics in patients with amelogenesis imperfecta can be complicated by commonly occurring dental features in this group as well as patient factors. In this article we examine ways to avoid the common pitfalls of orthodontic management and the importance of adequate and timely liaison between the general dental practitioner and the multidisciplinary team.

  12. Dentinogenesis imperfecta: endodontic implications. Case report.

    Science.gov (United States)

    Pettiette, M T; Wright, J T; Trope, M

    1998-12-01

    Dentinogenesis imperfecta is a hereditary disorder resulting in defective dentin in both the primary and secondary dentitions. The complications of dentinogenesis imperfecta are difficult to manage and provide a challenge to the dentist. This case report concerns treating an African American patient with dentinogenesis imperfecta who appeared for treatment with endodontic pathosis. It illustrates the need for appropriate and timely restorative treatment to prevent pulpal pathosis. Also demonstrated is the difficulty of endodontically treating dentinogenesis imperfecta teeth because of pulpal obliteration and abnormal dentin mineralization. Early and correct diagnosis of dentinogenesis imperfecta is imperative to enable appropriate preventive interventions and optimal dental treatment. Although pulpal pathosis is rarely reported with dentinogenesis imperfecta, endodontic treatment is occasionally necessary and has a guarded prognosis if initiated after pulp canal obliteration has occurred.

  13. AMELOGENESIS IMPERFECTA: A CLINICAL REPORT

    Directory of Open Access Journals (Sweden)

    Veena

    2015-01-01

    Full Text Available AIM: This clinical case report describes the oral rehabilitation of a young adult female patient diagnosed with hypoplastic Amelogenesis imperfecta. SUMMARY : Amelogenesis Imperfecta is a hereditary condition that affects the formation of the enamel mineralization process of both the primary and secondary dentition. It is clinically and genetically heterogeneous grou p of condition that affects both the quantity and quality of the enamel structure resulting in extensive loss of tooth tissue , poor esthetics and tooth sensitivity. The main objective for the selected treatment was to enhance the esthetics , and restoring m asticatory function. Treatment was divided into phases which included removal of impacted canine , lengthening of the maxillary and mandibular clinical crowns , and placement of anterior and posterior crowns.

  14. Hereditary dentine disorders: dentinogenesis imperfecta and dentine dysplasia.

    Science.gov (United States)

    Barron, Martin J; McDonnell, Sinead T; Mackie, Iain; Dixon, Michael J

    2008-11-20

    The hereditary dentine disorders, dentinogenesis imperfecta (DGI) and dentine dysplasia (DD), comprise a group of autosomal dominant genetic conditions characterised by abnormal dentine structure affecting either the primary or both the primary and secondary dentitions. DGI is reported to have an incidence of 1 in 6,000 to 1 in 8,000, whereas that of DD type 1 is 1 in 100,000. Clinically, the teeth are discoloured and show structural defects such as bulbous crowns and small pulp chambers radiographically. The underlying defect of mineralisation often results in shearing of the overlying enamel leaving exposed weakened dentine which is prone to wear. Currently, three sub-types of DGI and two sub-types of DD are recognised but this categorisation may change when other causative mutations are found. DGI type I is inherited with osteogenesis imperfecta and recent genetic studies have shown that mutations in the genes encoding collagen type 1, COL1A1 and COL1A2, underlie this condition. All other forms of DGI and DD, except DD-1, appear to result from mutations in the gene encoding dentine sialophosphoprotein (DSPP), suggesting that these conditions are allelic. Diagnosis is based on family history, pedigree construction and detailed clinical examination, while genetic diagnosis may become useful in the future once sufficient disease-causing mutations have been discovered. Differential diagnoses include hypocalcified forms of amelogenesis imperfecta, congenital erythropoietic porphyria, conditions leading to early tooth loss (Kostmann's disease, cyclic neutropenia, Chediak-Hegashi syndrome, histiocytosis X, Papillon-Lefevre syndrome), permanent teeth discolouration due to tetracyclines, Vitamin D-dependent and vitamin D-resistant rickets. Treatment involves removal of sources of infection or pain, improvement of aesthetics and protection of the posterior teeth from wear. Beginning in infancy, treatment usually continues into adulthood with a number of options including

  15. Hereditary dentine disorders: dentinogenesis imperfecta and dentine dysplasia

    Directory of Open Access Journals (Sweden)

    MacKie Iain

    2008-11-01

    Full Text Available Abstract The hereditary dentine disorders, dentinogenesis imperfecta (DGI and dentine dysplasia (DD, comprise a group of autosomal dominant genetic conditions characterised by abnormal dentine structure affecting either the primary or both the primary and secondary dentitions. DGI is reported to have an incidence of 1 in 6,000 to 1 in 8,000, whereas that of DD type 1 is 1 in 100,000. Clinically, the teeth are discoloured and show structural defects such as bulbous crowns and small pulp chambers radiographically. The underlying defect of mineralisation often results in shearing of the overlying enamel leaving exposed weakened dentine which is prone to wear. Currently, three sub-types of DGI and two sub-types of DD are recognised but this categorisation may change when other causative mutations are found. DGI type I is inherited with osteogenesis imperfecta and recent genetic studies have shown that mutations in the genes encoding collagen type 1, COL1A1 and COL1A2, underlie this condition. All other forms of DGI and DD, except DD-1, appear to result from mutations in the gene encoding dentine sialophosphoprotein (DSPP, suggesting that these conditions are allelic. Diagnosis is based on family history, pedigree construction and detailed clinical examination, while genetic diagnosis may become useful in the future once sufficient disease-causing mutations have been discovered. Differential diagnoses include hypocalcified forms of amelogenesis imperfecta, congenital erythropoietic porphyria, conditions leading to early tooth loss (Kostmann's disease, cyclic neutropenia, Chediak-Hegashi syndrome, histiocytosis X, Papillon-Lefevre syndrome, permanent teeth discolouration due to tetracyclines, Vitamin D-dependent and vitamin D-resistant rickets. Treatment involves removal of sources of infection or pain, improvement of aesthetics and protection of the posterior teeth from wear. Beginning in infancy, treatment usually continues into adulthood with a

  16. Neridronato nel trattamento dell’osteogenesi imperfetta: prestazioni cliniche ed economiche di un farmaco orfano

    Directory of Open Access Journals (Sweden)

    Orietta Zaniolo

    2004-09-01

    Full Text Available Bisphosphonates (BPs are osteoclast-mediated bone resorption inhibitors and the nature of the groups attached to the central carbon atom determines the drug potency. Neridronate is an injectable aminobisphosphonate, structurally similar to alendronate and pamidronate, authorized for the treatment of osteogenesis imperfecta (OI. This drug has often been used to treat other pathologies, as an off-label option, to increase tolerability and ameliorate compliance, partly because the management of orally administered bisphosphonates, with their gastrointestinal side effects, results complicated. In this paper pharmacokinetic, pharmacodinamic and main placebo-controlled clinical trials on OI patients are reviewed. The available scientific evidence demonstrates the neridronate efficacy to improve spine and hip bone mineral density, to lower markers of skeletal turnover and to decrease fracture incidence, compared with controls. We also report clinical trials results and data about the effect of intravenous infusions of neridronate in patients with postmenopausal osteoporosis, Paget’s disease and rheumatoid arthritis. Finally, we consider the economical impact of chronic and incapacitating pathologies, like osteogenesis imperfecta, on family’s total income and the influence of the disease on quality of life of pediatric and adult patients.

  17. Craniofacial distraction osteogenesis.

    Science.gov (United States)

    Winters, Ryan; Tatum, Sherard A

    2014-11-01

    Distraction osteogenesis (DO) may be the most versatile tool to become available to the craniofacial surgeon in recent years. It can be used in an ever-expanding register of clinical scenarios and offers major advantages over conventional craniofacial techniques in some circumstances. Craniofacial surgery has significant complications, some of which can be mitigated but not eliminated by choosing DO over conventional approaches. Although some DO applications are in their infancy with limited data, this article provides an overview of current uses of this versatile technology.

  18. A study of dentinogenesis imperfecta

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Eui Whan [Dept. of Oral Radiology, College of Dentistry, Chosun University, Kwangju (Korea, Republic of)

    1992-08-15

    The author observed a case of dentinogenesis imperfecta in a 8-year-old and a 9-year old brother with complaints of abnormal morphologic changes of the teeth. 1. Clinically, yellowish brown colored teeth, fractured crown and numerous retained root tips of edciduous teeth with severe attrition were observed in the both deciduous and permanent dentitions. 2. Radiographically, small-sized teeth partial or complete obliteration of the pulp chambers and pulp canals in the anterior teeth, partial obliteration of the pulp chambers and thin enamel in the permanent tooth germs were observed. 3. The familial history was their father has been lose his teeth early.

  19. Combined Treatment with Laser Sintering and Zirconium: A Case Report of Dentinogenesis Imperfecta

    Directory of Open Access Journals (Sweden)

    Simel Ayyildiz

    2013-01-01

    Full Text Available Osteogenesis imperfecta (OI is a heterogeneous disorder of connective tissue that manifests mainly as skeletal deformity and bone fragility. Dentinogenesis imperfecta (DI is sometimes an accompanying symptom of OI. The treatment protocol of these patients varies according to the clinical appearance. The case report here describes complete mouth rehabilitation of an 18-year-old male patient with OI and DI using direct metal laser sintering (DMLS technique of metal-ceramic restorations and zirconium all-ceramic crowns. DMLS is an additive metal fabrication technology that is simpler, more precise, and healthier than conventional manufacturing and can be remarkably cost effective. Moreover, the technique affords highly accurate production of fixed partial dentures with ideal marginal fit and excellent mechanical properties. The patient was treated using a multidisciplinary strategy that focused on controlling caries, protecting teeth from further wear, obtaining an appropriate vertical dimension, and providing soft tissue support to return the facial profile to a normal appearance using new technology in the field of prosthetics.

  20. Combined treatment with laser sintering and zirconium: a case report of dentinogenesis imperfecta.

    Science.gov (United States)

    Ayyildiz, Simel; Sahin, Cem; Akgün, Ozlem Marti; Basak, Feridun

    2013-01-01

    Osteogenesis imperfecta (OI) is a heterogeneous disorder of connective tissue that manifests mainly as skeletal deformity and bone fragility. Dentinogenesis imperfecta (DI) is sometimes an accompanying symptom of OI. The treatment protocol of these patients varies according to the clinical appearance. The case report here describes complete mouth rehabilitation of an 18-year-old male patient with OI and DI using direct metal laser sintering (DMLS) technique of metal-ceramic restorations and zirconium all-ceramic crowns. DMLS is an additive metal fabrication technology that is simpler, more precise, and healthier than conventional manufacturing and can be remarkably cost effective. Moreover, the technique affords highly accurate production of fixed partial dentures with ideal marginal fit and excellent mechanical properties. The patient was treated using a multidisciplinary strategy that focused on controlling caries, protecting teeth from further wear, obtaining an appropriate vertical dimension, and providing soft tissue support to return the facial profile to a normal appearance using new technology in the field of prosthetics.

  1. Distraction Osteogenesis Update: Introduction of Multidirectional Cranial Distraction Osteogenesis.

    Science.gov (United States)

    Gomi, Akira; Sunaga, Ataru; Kamochi, Hideaki; Oguma, Hirofumi; Sugawara, Yasushi

    2016-05-01

    In this review, we discuss in detail our current procedure for treating craniosynostosis using multidirectional cranial distraction osteogenesis (MCDO). The MCDO method allows all phenotypes of skull deformity to be reshaped by distraction osteogenesis, except in patients who are 5 months of age or younger and patients with posterior cranial vault problems. We report the results of clinical data of 36 children with craniosynostosis who underwent MCDO between 2005 and 2014 in our institute. This method has the following benefits, such as a high flexibility of reshaping, shorter treatment period and less invasive secondary intervention. We also discuss the other distraction osteogenesis techniques that are used to treat craniosynostosis and compare them with MCDO. The preferred procedure for correction of craniosynostosis may depend on the patient's age, the extent of deformity, and the extent of correction achievable by surgery. We can arrange the combinations of various methods according to the advantage and disadvantage of each technique.

  2. Mandibular midline distraction osteogenesis.

    Science.gov (United States)

    Botzenhart, Ute Ulrike; Végh, András; Jianu, Rodica; Gedrange, Tomasz

    2013-12-01

    In orthodontics, bone structure, its density and dimensions play an essential role by explaining limitations in magnitude, size and extent of tooth movement. Severe anterior crowding is one of the most frequently encountered dental malocclusions. Its therapy is mostly limited by lack of basal and alveolar bone and it often involves tooth extractions. Mandibular midline distraction osteogenesis is a method of natural bone generation and also a treatment option to achieve space regaining in a much-reduced lower jaw with distinctive frontal place deficit and severe anterior crowding, without sacrificing permanent teeth. McCarthy and Guerrero were of the first researchers reporting on this method applied on human lower jaws and they increased clinical interest in this approach. Although this method has been clinically used ever since, many questions concerning effects on bone regeneration speed, bone quality, tooth movement into regenerated area, periodontal health and long-time stability of treatment outcomes have not been sufficiently investigated. This overview should present the current clinical and biological state of knowledge about bone gain and tooth movement through regenerate bone. Furthermore it should encourage interest in further research on this topic.

  3. Dentinogenesis imperfecta: the importance of early treatment.

    Science.gov (United States)

    Delgado, Antonio Carlos; Ruiz, Matilde; Alarcón, Jose Antonio; González, Encarnación

    2008-03-01

    Dentinogenesis imperfecta, also known as hereditary opalescent dentin, is a dentin development disorder with autosomal dominant transmission that affects both the primary and permanent dentition. A case is reported of a family in which the mother and her 6- and 20-year-old children were diagnosed with dentinogenesis imperfecta type II. The mouths of these patients illustrate the progressive deterioration of affected teeth if not adequately treated. The treatment of the 6-year-old son is described, and therapeutic approaches to this disorder in primary and permanent dentition are reviewed. This family exemplifies the need for the earliest possible diagnosis and treatment of dentinogenesis imperfecta to prevent extensive deterioration of the dentition and occlusion.

  4. Enamel formation and amelogenesis imperfecta.

    Science.gov (United States)

    Hu, Jan C-C; Chun, Yong-Hee P; Al Hazzazzi, Turki; Simmer, James P

    2007-01-01

    Dental enamel is the epithelial-derived hard tissue covering the crowns of teeth. It is the most highly mineralized and hardest tissue in the body. Dental enamel is acellular and has no physiological means of repair outside of the protective and remineralization potential provided by saliva. Enamel is comprised of highly organized hydroxyapatite crystals that form in a defined extracellular space, the contents of which are supplied and regulated by ameloblasts. The entire process is under genetic instruction. The genetic control of amelogenesis is poorly understood, but requires the activities of multiple components that are uniquely important for dental enamel formation. Amelogenesis imperfecta (AI) is a collective designation for the variety of inherited conditions displaying isolated enamel malformations, but the designation is also used to indicate the presence of an enamel phenotype in syndromes. Recently, genetic studies have demonstrated the importance of genes encoding enamel matrix proteins in the etiology of isolated AI. Here we review the essential elements of dental enamel formation and the results of genetic analyses that have identified disease-causing mutations in genes encoding enamel matrix proteins. In addition, we provide a fresh perspective on the roles matrix proteins play in catalyzing the biomineralization of dental enamel.

  5. Bone regeneration during distraction osteogenesis

    NARCIS (Netherlands)

    Amir, L.R.; Everts, V.; Bronckers, A.L.J.J.

    2009-01-01

    Bone has the capacity to regenerate in response to injury. During distraction osteogenesis, the renewal of bone is enhanced by gradual stretching of the soft connec- tive tissues in the gap area between two separated bone segments. This procedure has received much clinical atten- tion as a way to co

  6. Multiple unerupted teeth with amelogenesis imperfecta in siblings.

    Science.gov (United States)

    Hegde, Shruthi

    2012-05-01

    Amelogenesis imperfecta encompasses a group of inherited abnormalities that are generally considered to primarily affect the formation and/or calcification of enamel. This case report describes the unusual presentation of amelogenesis imperfecta in siblings as multiple unerupted teeth, multiple pulpal calcifications, and multiple dilacerations of roots along with the defect in the enamel. The intent of our report is to highlight a rare co-occurrence of amelogenesis imperfecta with multiple morphologic alterations in siblings.

  7. Multiple Unerupted Teeth with Amelogenesis Imperfecta in Siblings

    Directory of Open Access Journals (Sweden)

    Shruthi Hegde

    2012-01-01

    Full Text Available Amelogenesis imperfecta encompasses a group of inherited abnormalities that are generally considered to primarily affect the formation and/or calcification of enamel. This case report describes the unusual presentation of amelogenesis imperfecta in siblings as multiple unerupted teeth, multiple pulpal calcifications, and multiple dilacerations of roots along with the defect in the enamel. The intent of our report is to highlight a rare co-occurrence of amelogenesis imperfecta with multiple morphologic alterations in siblings.

  8. Study on the Pathogenic Gene of Dentinogenesis Imperfecta of Type Ⅱ%Ⅱ型牙本质发育不全的致病基因研究进展

    Institute of Scientific and Technical Information of China (English)

    吴柒柱; 吉日木图; 齐玥; 陈宇杰; 刘海平; 白海花

    2009-01-01

    牙本质发育不全症是一种常染色体显性遗传病,其致病基因定位于4q2l.临床上分为三型:Ⅰ型(Dentinogenesis Imperfecta type Ⅰ, DGI-Ⅰ) 主要见于成骨发育不全(Osteogenesis Imperfecta, OI)患者的口腔,其病因被广泛认为是由Ⅰ型胶原基因突变导致.Ⅲ型(Dentinogenesis Imperfecta type Ⅲ, DGI-Ⅲ)是一种特殊的遗传性牙本质发育不全,在美国马里兰州的3个隔离民族群中独立发生.Ⅱ型(Dentinogenesis Imperfecta typeⅡ, DGI-Ⅱ)在临床上最为常见,成为研究热点.Ⅱ型牙本质发育不全的致病基因主要为牙本质唾液酸焦磷酸蛋白基因(dentin sialophosphoprotein, DSPP)突变引起,独立发生且具有高度的遗传异质性.主要对牙本质发育不全Ⅱ型的候选基因及DSPP的突变进行了综述.

  9. 成骨不全1例报告%One case: osteogenesis imperfecta

    Institute of Scientific and Technical Information of China (English)

    赵立; 郑俊

    2007-01-01

    临床资料 患儿,男性,出生3d,体重2.7kg,身长50cm,头围32.5cm,前囟4cm×4cm,后囟5cm×5cm,头颅软化,触之似乒乓球,胸围32cm。四肢短粗,弯曲,足内翻,蓝色巩膜,实验室检查:血钙、血磷、碱性磷酸酶均正常。

  10. Adults with Osteogenesis Imperfecta%患成骨不全的成人

    Institute of Scientific and Technical Information of China (English)

    许诺

    2007-01-01

    成骨不全是一种遗传病,由编码Ⅰ型胶原的基因的突变导致。成骨不全的Sillence分类(Ⅰ~Ⅳ型)是根据该病的临床特征进行的分类。一项临床试验纳入成骨不全的成人,我们使用双能X线吸收仪获得其全身影,可见广谱的骨骼表现,从骨骼轻度异常(患Ⅰ型成骨不全的38岁妇女)到严重变形(患Ⅲ型成骨不全的40岁男性)。

  11. The diagnosis of osteogenesis imperfecta%成骨不全的X线诊断

    Institute of Scientific and Technical Information of China (English)

    李大鹏; 刘凯; 邱询花; 许玉军

    2006-01-01

    目的:探讨成骨不全的X线表现,提高对本病的诊断正确率.方法:回顾性分析了成骨不全的临床X线表现8例.结果:8例均有骨质疏松、骨皮质变薄,骨干细长6例,骨干增粗2例,肢体明显畸形4例,椎体内凹5例,脊柱弯曲畸形5例,干骺致密横行线3例,肋骨变细4例,骨折8例(100%),蓝色巩膜6例(75%),听力障碍5例(62.5%).结论:本病为骨发育障碍性疾病,X线检查对本病的诊断有着十分重要的价值.

  12. OI Issues: Type I - Understanding the Mildest Form of Osteogenesis Imperfecta

    Science.gov (United States)

    ... people. Managing and Treating Type I OI in Adults Osteoporosis (low bone density) is an almost universal consequence ... are approved by FDA for preventing and treating osteoporosis in adults. The goal is to prevent additional loss of ...

  13. Study in Mice Links Key Signaling Molecule to Underlying Cause of Osteogenesis Imperfecta

    Science.gov (United States)

    ... on Research 2014 August 2014 (historical) Study in Mice Links Key Signaling Molecule to Underlying Cause of ... genetic disease characterized by fragile bones. Working in mice, the researchers found that TGF-β, a molecule ...

  14. Amelogenesis imperfecta and localised aggressive periodontitis: A rare clinical entity

    Directory of Open Access Journals (Sweden)

    Gayatri Gundannavar

    2013-01-01

    Full Text Available This case report presents two female patients whose chief complaint was discoloration of teeth. On careful clinical examination it was found that the patients had features of amelogenesis imperfecta and localised aggressive periodontitis. This article will give an insight of clinical and radiographic features of amelogenesis imperfecta with localised aggressive periodontitis, which is a rare clinical entity.

  15. Amelogenesis imperfecta and localised aggressive periodontitis: A rare clinical entity.

    Science.gov (United States)

    Gundannavar, Gayatri; Rosh, Radhika M; Chandrasekaran, Shoba; Hussain, Ahad M

    2013-01-01

    This case report presents two female patients whose chief complaint was discoloration of teeth. On careful clinical examination it was found that the patients had features of amelogenesis imperfecta and localised aggressive periodontitis. This article will give an insight of clinical and radiographic features of amelogenesis imperfecta with localised aggressive periodontitis, which is a rare clinical entity.

  16. [Distraction osteogenesis: principles, history and background

    NARCIS (Netherlands)

    Vissink, A.; Baat, C. de

    2008-01-01

    Distraction osteogenesis is a treatment in which new bone is created in the space which comes to exist between bone fragments that have slowly been driven apart by osteogenesis. This treatment, originally developed in orthopaedic surgery, is also commonly used for correcting deformities in the head

  17. Alveolar distraction osteogenesis – Crestal widening by distraction osteogenesis

    Directory of Open Access Journals (Sweden)

    Zvi Laster

    2010-04-01

    Full Text Available Following tooth extraction, resorption of the residual ridges occurs in both the vertical and the horizontal directions. Most of this resorption occurs within the first 6 months after tooth extraction. To correc tthis vertical/ horizontal/ dual situation, several surgical approaches have been proposed: autogenous bone grafts, guided bone regeneration, and alveolar distraction osteogenesis (ADO. In recent years, ADO has gained an ongoing popularity ,especially in view of its numerous advantages, mostimportant among them being the shortening of treatment periods and earlier dental implant placement. In cases in which there is sufficient vertical height but not enough bucco-ligual width to accommodate an implant, crestal width has to be built. Crestal widening by distraction osteogenesis is the preferred technique in suchcases. In this study a new type of crest widener, the"Laster" Crest Widening Distractor, is presented, reporting two cases where crest widening by distraction was chosen as the preferred treatment plan. Finally the main advantages and disadvantages of the new crest widening distractor are discussed, helping thus the clinician to make up his mind about this new promising device and surgical technique.

  18. Osteogensis imperfecta type I is commonly due to a COLIAI null allel of type I collagen

    Energy Technology Data Exchange (ETDEWEB)

    Willing, M.C.; Pruchno, C.J. (Univ. of Iowa, Iowa City, IA (United States)); Atkinson, M.; Byers, P.H. (Univ. of Washington, Seattle, WA (United States))

    1992-09-01

    Dermal fibroblasts from most individuals with osteogenesis imperfecta (OI) type I produce about half the normal amount of type I procollagen, as a result of decreased synthesis of one of its constituent chains, pro[alpha](I). To test the hypothesis that decreased synthesis of pro[alpha](I) chains results from mutations in the COL1A1 gene, the authors used primer extension with nucleotide-specific chain termination to measure the contribution of individual COL1A1 alleles to the mRNA pool in fibroblasts from affected individuals. A polymorphic Mn/I restriction endonuclease site in the 3'-untranslated region of COL1A1 was used to distinguish the transcripts of the two alleles in heterozygous individuals. Twenty-three individuals from 21 unrelated families were studied. In each case there was marked diminution in steady-state mRNA levels from one COL1A2 allele. Loss of an allele through deletion or rearrangement was not the cause of the diminished COL1A1 mRNA levels. Primer extension with nucleotide-specific chain termination allows identification of the mutant COL1A1 allele in cell strains that are heterozygous for an expressed polymorphism. It is applicable to sporadic cases, to small families, and to large families in whom key individuals are uninformative at the polymorphic sites used in linkage analysis, making it a useful adjunct to the biochemical screening of collagenous proteins for OI. 40 refs., 3 figs., 1 tab.

  19. Amelogenesis imperfecta: review of diagnostic findings and treatment concepts.

    Science.gov (United States)

    Sabandal, Martin M I; Schäfer, Edgar

    2016-09-01

    Mineralization defects like amelogenesis imperfecta are often of hereditary origin. This article reviews the diagnostic findings and summarizes the suggested treatment approaches. Currently, there are no defined therapy recommendations available for patients suffering from amelogenesis imperfecta. The mentioned therapies are more or less equal but no comprehensive therapy recommendation is evident. When treating patients suffering from amelogenesis imperfecta, a comprehensive therapy of almost every dental discipline has to be considered. The earlier the diagnosis of amelogenesis imperfecta is confirmed, the better the outcome is. Optimal treatment approaches consist of early diagnosis and treatment approach and frequent dental recall appointments to prevent progressive occlusal wear or early destruction by caries. Full-mouth prosthetic treatment seems to be the best treatment option.

  20. Amelogenesis Imperfecta with Coronal Resorption: Report of Three Cases.

    Science.gov (United States)

    Bhatia, Shannu K; Hunter, M Lindsay; Ashley, Paul F

    2015-12-01

    Intracoronal resorption of the permanent dentition in cases of amelogenesis imperfecta (AI) is a rare finding which poses an added complication to the already complex management of this condition. This paper presents three cases of AI associated with delayed eruption of permanent teeth in which asymptomatic intracoronal resorption occurred. CPD/Clinical Relevance: This paper highlights the fact that teeth affected with amelogenesis imperfecta may undergo asymptomatic intracoronal resorption which is only identifiable radiographically.

  1. Interradicular dentin dysplasia associated with amelogenesis imperfecta with taurodontism or trichodentoosseous syndrome: A diagnostic dilemma

    Directory of Open Access Journals (Sweden)

    Veda Hegde

    2014-01-01

    Full Text Available Amelogenesis imperfecta is a hereditary disorder with diverse clinical presentation, where enamel is the tissue that is primarily affected either quantitatively or qualitatively. Hypomaturation/hypoplastic amelogenesis imperfecta with taurodontism is a rare variant of amelogenesis imperfecta which is often confused with trichodentoosseous syndrome. We report a rare case of hereditary enamel defect with taurodontism associated with interradicular dentin dysplasia.

  2. Interradicular dentin dysplasia associated with amelogenesis imperfecta with taurodontism or trichodentoosseous syndrome: a diagnostic dilemma.

    Science.gov (United States)

    Hegde, Veda; Srikanth, K

    2014-01-01

    Amelogenesis imperfecta is a hereditary disorder with diverse clinical presentation, where enamel is the tissue that is primarily affected either quantitatively or qualitatively. Hypomaturation/hypoplastic amelogenesis imperfecta with taurodontism is a rare variant of amelogenesis imperfecta which is often confused with trichodentoosseous syndrome. We report a rare case of hereditary enamel defect with taurodontism associated with interradicular dentin dysplasia.

  3. Enamelin and autosomal-dominant amelogenesis imperfecta.

    Science.gov (United States)

    Hu, J C-C; Yamakoshi, Y

    2003-01-01

    Dental enamel forms as a progressively thickening extracellular layer by the action of proteins secreted by ameloblasts. The most abundant enamel protein is amelogenin, which is expressed primarily from a gene on the X-chromosome (AMELX). The two most abundant non-amelogenin enamel proteins are ameloblastin and enamelin, which are expressed from the AMBN and ENAM genes, respectively. The human AMBN and ENAM genes are located on chromosome 4q13.2. The major secretory products of the human AMELX, AMBN, and ENAM genes have 175, 421, and 1103 amino acids, respectively, and are all post-translationally modified, secreted, and processed by proteases. Mutations in AMELX have been shown to cause X-linked amelogenesis imperfecta (AI), which accounts for 5% of AI cases. Mutations in ENAM cause a severe form of autosomal-dominant smooth hypoplastic AI that represents 1.5%, and a mild form of autosomal-dominant local hypoplastic AI that accounts for 27% of AI cases in Sweden. The discovery of mutations in the ENAM gene in AI kindreds proved that enamelin is critical for proper dental enamel formation and that it plays a role in human disease. Here we review how enamelin was discovered, what is known about enamelin protein structure, post-translational modifications, processing by proteases, and its potentially important functional properties such as its affinity for hydroxyapatite and influence on crystal growth in vitro. The primary structures of human, porcine, mouse, and rat enamelin are compared, and the human enamelin gene, its structure, chromosomal localization, temporal and spatial patterns of expression, and its role in the etiology of amelogenesis imperfecta are discussed.

  4. Transcriptional repression of the Dspp gene leads to dentinogenesis imperfecta phenotype in Col1a1-Trps1 transgenic mice.

    Science.gov (United States)

    Napierala, Dobrawa; Sun, Yao; Maciejewska, Izabela; Bertin, Terry K; Dawson, Brian; D'Souza, Rena; Qin, Chunlin; Lee, Brendan

    2012-08-01

    Dentinogenesis imperfecta (DGI) is a hereditary defect of dentin, a calcified tissue that is the most abundant component of teeth. Most commonly, DGI is manifested as a part of osteogenesis imperfecta (OI) or the phenotype is restricted to dental findings only. In the latter case, DGI is caused by mutations in the DSPP gene, which codes for dentin sialoprotein (DSP) and dentin phosphoprotein (DPP). Although these two proteins together constitute the majority of noncollagenous proteins of the dentin, little is known about their transcriptional regulation. Here we demonstrate that mice overexpressing the Trps1 transcription factor (Col1a1-Trps1 mice) in dentin-producing cells, odontoblasts, present with severe defects of dentin formation that resemble DGI. Combined micro-computed tomography (µCT) and histological analyses revealed tooth fragility due to severe hypomineralization of dentin and a diminished dentin layer with irregular mineralization in Col1a1-Trps1 mice. Biochemical analyses of noncollagenous dentin matrix proteins demonstrated decreased levels of both DSP and DPP proteins in Col1a1-Trps1 mice. On the molecular level, we demonstrated that sustained high levels of Trps1 in odontoblasts lead to dramatic decrease of Dspp expression as a result of direct inhibition of the Dspp promoter by Trps1. During tooth development Trps1 is highly expressed in preodontoblasts, but in mature odontoblasts secreting matrix its expression significantly decreases, which suggests a Trps1 role in odontoblast development. In these studies we identified Trps1 as a potent inhibitor of Dspp expression and the subsequent mineralization of dentin. Thus, we provide novel insights into mechanisms of transcriptional dysregulation that leads to DGI.

  5. Leader genes in osteogenesis: a theoretical study.

    Science.gov (United States)

    Orlando, Bruno; Giacomelli, Luca; Ricci, Massimiliano; Barone, Antonio; Covani, Ugo

    2013-01-01

    Little is still known about the molecular mechanisms involved in the process of osteogenesis. In this paper, the leader genes approach, a new bioinformatics method which has already been experimentally validated, is adopted in order to identify the genes involved in human osteogenesis. Interactions among genes are then calculated and genes are ranked according to their relative importance in this process. In total, 167 genes were identified as being involved in osteogenesis. Genes were divided into 4 groups, according to their main function in the osteogenic processes: skeletal development; cell adhesion and proliferation; ossification; and calcium ion binding. Seven genes were consistently identified as leader genes (i.e. the genes with the greatest importance in osteogenesis), while 14 were found to have slightly less importance (class B genes). It was interesting to notice that the larger part of leader and class B genes belonged to the cell adhesion and proliferation or to the ossification sub-groups. This finding suggested that these two particular sub-processes could play a more important role in osteogenesis. Moreover, among the 7 leader genes, it is interesting to notice that RUNX2, BMP2, SPARC, PTH play a direct role in bone formation, while the 3 other leader genes (VEGF, IL6, FGF2) seem to be more connected with an angiogenetic process. Twenty-nine genes have no known interactions (orphan genes). From these results, it may be possible to plan an ad hoc experimentation, for instance by microarray analyses, focused on leader, class B and orphan genes, with the aim to shed new light on the molecular mechanisms underlying osteogenesis.

  6. Long-term treatment of osteogenesis imperfects tarda in adults with salmon calcitonin and calcium

    Energy Technology Data Exchange (ETDEWEB)

    Zanzi, I.; Wallach, S.; Ellis, K.J.; Aloia, J.F.; Atkins, H.L.; Cohn, S.H.

    1976-02-01

    Three postmenopausal women with osteogenesis imperfecta (O.I.) tarda were treated with daily salmon calcitonin (sCT) and calcium supplements for 12 to 33 months. Total body calcium (TBCa) measured by total body neutron activation analysis revealed a marked deficit exceeding that of severely osteoporotic women. In one patient a rapid loss of TBCa of 5 percent at five months of treatment was partially reversed after twelve months of treatment. In eight subsequent months of Ca supplementation alone, the loss of TBCa resumed and amounted to 11 percent. The second patient increased TBCa by 9 percent after a total of 33 months of sCT and Ca supplementation. The third patient also showed a rapid decrease in TBCa of 8 percent during one year of sCT and Ca, but she was also receiving systemic corticosteroids for asthma. Her TBCa recovered to 8 percent above baseline eight months after stopping sCT, continuation of the Ca and a drastic decrease in the dose of corticosteroids. The action of sCT in this patient might have been impaired by the concomitant administration of corticosteroids. Urinary hydroxyproline decreased from initial normal values in two patients suggesting continued inhibition of bone resorption. The results confirm previous work using calcitonin in children with O.I. and suggest that sCT may also be of benefit in adults with O.I. (auth)

  7. El poder en la paz imperfecta y en Foucault

    Directory of Open Access Journals (Sweden)

    Cássia M. Rosato

    2012-04-01

    Full Text Available Este trabajo debate el concepto de poder en la paz imperfecta y en la obra de Foucault. El objetivo principal es demostrar que la perspectiva foucaultiana del poder no está lejos de la noción de poder en la paz imperfecta propuesta por Muñoz. Para tanto, ese artículo empieza con la idea de paz de UNESCO y el contexto sociopolítico que favoreció el surgimiento de esa concepción. Enseguida, presenta características de la paz imperfecta, así como el concepto de poder está inserido en esta proposición y en Foucault. Al final, apunta tres semejanzas y/o aproximaciones existentes entre ambas las orientaciones que confirman su cercanía.

  8. Interdisciplinary approach to oral rehabilitation of patient with amelogenesis imperfecta.

    Science.gov (United States)

    Yilmaz, Burak; Oz, Ulas; Yilmaz, Hasan Guney

    2014-03-01

    Amelogenesis imperfecta is a hereditary condition that affects the development of enamel, causing quantity, structural and compositional anomalies that involve all dentitions. Consequently, the effects can extend to both the primary and secondary dentitions. Patients with amelogenesis imperfecta may present with clinical difficulties, such as insufficient crown length, tooth sensitivity and orthodontic discrepancies, all of which can be resolved successfully with an interdisciplinary approach. This case report describes the interdisciplinary approach to the treatment of a 22-year-old patient with amelogenesis imperfecta. The proper alignment of anterior teeth and gingivo-cervical line was provided with orthodontic and periodontal treatments. All-ceramic crowns were placed on anterior, and metal-ceramic restorations were placed on posterior teeth to reduce sensitivity and improve esthetics with function. Improved esthetic appearance, reduced tooth sensitivity and the resolution of a potentially harmful psychosocial condition were achieved. Patient remained satisfied in the 12-month follow-up examination.

  9. Dentinogenesis imperfecta: long-term rehabilitation in a child.

    Science.gov (United States)

    Bouvier, Dominique; Leheis, Benoît; Duprez, Jean-Pierre; Bittar, Elias; Coudert, Jean-Loup

    2008-01-01

    The treatment of dentinogenesis imperfecta represents a challenge for the dental practitioner. The aim of this case report was to describe the chronology and problems encountered in the long-term rehabilitation of a young girl suffering from dentinogenesis imperfecta with severe attrition. A 2-stage treatment over a period of 9 years is described and discussed. This treatment comprised an initial treatment to restore esthetic appearance and function during primary and mixed dentitions and a complete prosthetic rehabilitation in a second stage to protect permanent teeth with low-fusion ceramicmetal individual crowns. Discovery of a follicular cyst is also reported and its treatment is described.

  10. Amelogenesis imperfecta and the treatment plan - interdisciplinary team approach.

    Science.gov (United States)

    Suchancova, B; Holly, D; Janska, M; Stebel, J; Lysy, J; Thurzo, A; Sasinek, S

    2014-01-01

    Amelogenesis imperfecta is a set of hereditary defects representing mainly the development defects of enamel without the presence of whole-body symptoms. Developmental disorders can manifest a complete absence of enamel, which is caused by improper differentiation of ameloblasts. This article describes the diagnosis and treatment of a patient with amelogenesis imperfecta, as well as the need for interdisciplinary cooperation to achieve the best possible morphological, skeletal, functional and aesthetic rehabilitation of the patients with this diagnosis. Furthermore, the article reviews literature dealing with other anomalies occurring in association with amelogenesis imperfect (Fig. 12, Ref. 20).

  11. Dentinogenesis imperfecta: an early treatment strategy.

    Science.gov (United States)

    Sapir, S; Shapira, J

    2001-01-01

    Dentinogenesis imperfecta (DI) type 2 is a disease inherited in a simple autosomal dominant mode. As soon as the teeth erupt the parents may notice the problem and look for a pediatric dentist's advice and treatment. Early diagnosis and treatment of DI is recommended, as it may prevent or intercept deterioration of the teeth and occlusion and improve esthetics. The purpose of this article is to present the objectives, treatment options, and problems encountered in the treatment of DI in the early primary dentition. A two-stage treatment of a toddler under general anesthesia is described and discussed. This paper recommends for severe cases of DI two treatment stages performed under general anesthesia. Stage 1 is early (around age 18-20 months) and is directed to covering the incisors with composite restorations and the first primary molars with preformed crowns. Stage 2 (around age 28-30 months) seeks to protect the second primary molars with preformed crowns and cover the canines with composite restorations.

  12. A Case of Dentinogenesis Imperfecta Treated with Submerged Root Technique.

    Science.gov (United States)

    Uday, Ginjupally; Chandar, Bhanu; Srilakshmi, J; Khaitan, Tanya; Babu, B Balaji

    2015-09-01

    Dentinogenesis imperfecta (DGI), an autosomal dominant trait, is one of the most common hereditary disorders affecting both the formation and mineralization of dentin. Either or both primary and permanent dentition is affected by it. Here, we present a case report of a 13-year-old female patient affected with DGI who had undergone prosthetic rehabilitation with submerged root technique.

  13. Rehabilitation of amelogenesis imperfecta using a reorganized approach: a case report.

    Science.gov (United States)

    Chan, Kingsley H C; Ho, Edward H T; Botelho, Michael G; Pow, Edmond H N

    2011-05-01

    Amelogenesis imperfecta is a genetic disorder that causes defective enamel development in both the primary and permanent dentitions. Significant tooth structure damage often results in various pulpal symptoms, occlusal disharmony, impaired function, and esthetic disfigurement. These problems pose great challenges to the clinician when rehabilitating patients with amelogenesis imperfecta. This case report describes an uncomplicated and logical way to reorganize, temporize, and completely restore an extensively damaged dentition caused by amelogenesis imperfecta.

  14. Bioceramics for osteogenesis, molecular and cellular advances.

    Science.gov (United States)

    Demirkiran, Hande

    2012-01-01

    The remarkable need for bone tissue replacement in clinical situations, its limited availability and some major drawbacks of autologous (from the patient) and allogeneic (from a donor) bone grafts are driving researchers to search for alternative approaches for bone repair. In order to develop an appropriate bone substitute, one should understand bone structure and properties and its growth, which will guide researchers to select the optimal conditions for tissue culture and implantation. It's well accepted that bioceramics are excellent candidates as bone replacement with osteogenesis, osteoinduction and osteoconduction capacity. Therefore, the molecular and cellular interactions that take place at the surface of bioceramics and their relevance in osteogenesis excites many researchers to delve deeper into this line of research.

  15. Amelogenesis imperfecta and anterior open bite: Etiological, classification, clinical and management interrelationships.

    Science.gov (United States)

    Alachioti, Xanthippi Sofia; Dimopoulou, Eleni; Vlasakidou, Anatoli; Athanasiou, Athanasios E

    2014-01-01

    Although amelogenesis imperfecta is not a common dental pathological condition, its etiological, classification, clinical and management aspects have been addressed extensively in the scientific literature. Of special clinical consideration is the frequent co-existence of amelogenesis imperfecta with the anterior open bite. This paper provides an updated review on amelogenesis imperfecta as well as anterior open bite, in general, and documents the association of these two separate entities, in particular. Diagnosis and treatment of amelogenesis imperfecta patients presenting also with anterior open bite require a lengthy, comprehensive and multidisciplinary approach, which should aim to successfully address all dental, occlusal, developmental, skeletal and soft tissue problems associated with these two serious clinical conditions.

  16. Characterization of the nanoscratch, microstructure, and composition in hypoplastic amelogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Ping Qing

    2015-07-01

    Full Text Available Hypoplastic amelogenesis imperfecta is a widespread hereditary disease that causes the loss of enamel. The purpose of this study was to investigate the nanoscratch resistance of hypoplastic amelogenesis imperfecta for providing a reference for restorative treatment. Four unerupted third molars from a patient diagnosed with hypoplastic amelogenesis imperfecta and seven unerupted third molars from normal individuals were compared. Atomic force microscopy and energy-dispersive X-ray spectroscopy were used to observe the microstructure and composition of the teeth (enamel and dentin. The nanoscratch tests of teeth (enamel and dentin were investigated using a nanoscratch tester, scanning electron microscopy, and a stylus profilometer. The results indicated that hypoplastic amelogenesis imperfecta teeth had different microstructures compared to normal teeth. Hypoplastic amelogenesis imperfecta demonstrated a higher composition of organic substance. Meanwhile, the friction coefficient of hypoplastic amelogenesis imperfecta was higher than that of normal teeth, and inferior frictional resistance of hypoplastic amelogenesis imperfecta teeth was observed. The main damaging mechanisms observed in hypoplastic amelogenesis imperfecta under nanoscratch were the combination of delamination, debris, and cracks in enamel with delamination, debris, and plastic deformation in dentin. Our findings suggested that new dental restorative materials should be selected to match the mechanical properties of hypoplastic amelogenesis imperfecta.

  17. Distraction osteogenesis in a severe mandibular deficiency

    Directory of Open Access Journals (Sweden)

    Ozyigit Aykut H

    2007-01-01

    Full Text Available Abstract Objective Distraction osteogenesis is an alternative treatment method for the correction of mandibular hypoplasia. In this case report, distraction with a multidirectional extraoral device was performed to gradually lengthen the corpus and ramus of a patient who had a severe hypoplastic mandible. Materials and methods The patient underwent bilateral extraoral ramus and corpus distraction osteogenesis. After seven days of latency period, distraction was performed 0.5 mm twice a day. Subsequent consolidation period was 12 weeks. Results The patient's mandible was elongated successfully. Cephalometric analysis revealed that ANB angle decreased from 13° to 6°, overjet of 15 mm decreased to 4 mm, corpus length increased from 49 mm to 67 mm, and ramus length increased from 41 mm to 43 mm. Posterior airway space (PAS also increased due to advancement of the mandible. In stereolithographic model evaluation it was determined that the distances from condylion to gonion and from gonion to pogonion increased. Conclusion Satisfactory results from both aesthetic and functional standpoints were obtained by distraction osteogenesis of the ramus and corpus.

  18. 成骨不全的影像学表现%The imageology manifestation of osteogenesis imperfecta

    Institute of Scientific and Technical Information of China (English)

    饶锡强; 丁海霞; 鲁植艳

    2008-01-01

    本文主要总结了成骨不全的一些影像学表现.包括X线、CT、MRI和超声检查.其中超声检查主要用于产前诊断.成骨不全的影像学特征主要有颅底凹陷征,增生性骨痂,骨折,骨量减少,Wormian骨,骨膜反应,干骺端硬化,骨形态改变,四肢关节改变以及脊柱侧凸等.根据其影像学特征及临床特点,能够对成骨不全作出早期诊断.

  19. Molecular genetics of osteogenesis imperfecta%成骨不全症的分子遗传学

    Institute of Scientific and Technical Information of China (English)

    刘怡; 李梅

    2013-01-01

    成骨不全症又称为脆骨病,是一种以骨骼脆性增加和骨量减少为特征的遗传性疾病.临床表现为反复骨折、蓝色巩膜、听力障碍、牙本质发育不良等.常染色体显性遗传成骨不全主要与骨基质蛋白Ⅰ型胶原合成障碍有关,而常染色体隐性遗传的成骨不全多与Ⅰ型胶原翻译后修饰或钙稳态相关,本文就成骨不全症的分子遗传学进展进行综述.

  20. Congenital osteogenesis imperfecta of neonates: Case report%新生儿先天性成骨不全1例

    Institute of Scientific and Technical Information of China (English)

    陈东雨; 李柏青

    2011-01-01

    @@ 患儿男,1个月,弃婴,因咳嗽、发热来院诊治.查体:体温38.4℃,呼吸34次/分,心率120次/分,体质量3.80 kg,体格发育正常,精神反应差,巩膜轻度偏蓝,活动少,手腕部下垂,双肺闻及中量水泡音,脊柱、四肢无畸形,双侧腹股沟见2.0 cm×2.0 cm包块,推之可还纳腹腔,肿物内可闻及肠鸣音.实验室检查:白细胞17.30×109/L、中性粒细胞比例68.30%、淋巴细胞比例25.40%、红细胞3.25×1012/L、血红蛋白72.00 g/L、血小板452×109/L.

  1. 新生儿成骨不全综合征1例%One case of neonatal osteogenesis imperfecta

    Institute of Scientific and Technical Information of China (English)

    林菊英

    2000-01-01

    @@ 患儿,女,第1胎,过期妊娠臀牵引助产娩出,出生时重度窒息,1 min Apgar评3分,3 min评7分.患儿头颅异常,左右面部不对称,左侧大于右侧,面部皮肤轻度发绀,蓝巩膜,多处畸形.1 h后全身骨骼X线(片号59382)摄片示:双侧锁骨、肋骨、肱骨、尺桡骨、胫腓骨骨干细长,骺端相对较大,且见多处新旧完全骨折.左侧股骨骨折,骨痂粗大,右侧股骨骨折,断端分离显著.双髋、左膝、右肘关节脱位.颅骨皮质菲薄且不连续,胸廓塌陷,仅见右下肺野小块透光区,左肺不张,见图1.诊断为:新生儿成骨不全综合征;左肺不张.患儿于生后第2天死亡. 

  2. Nuclear sequestration of COL1A1 mRNA transcript associated with type I osteogenesis imperfecta (OI)

    Energy Technology Data Exchange (ETDEWEB)

    Primorac, D.; Stover, M.L.; McKinstry, M.B. [and others

    1994-09-01

    Previously we identified an OI type I patient with a splice donor mutation that resulted in intron 26 retention instead of exon skipping and sequestration of normal levels of the mutant transcript in the nuclear compartment. Intron retention was consistent with the exon definition hypothesis for splice site selection since the size of the exon-intron-exon unit was less than 300 bp. Furthermore, the retained intron contained in-frame stop codons which is thought to cause the mutant RNA to remain within the nucleus rather than appearing in the cytoplasm. To test these hypotheses, genomic fragments containing the normal sequence or the donor mutation were cloned into a collagen minigene and expressed in stably tansfected NIH 3T3 cells. None of the modifications to the normal intron altered the level of RNA that accumulated in the cytoplasm, as expected. However none of the modifications to the mutant intron allowed accumulation of normal levels of mRNA in the cytoplasm. Moreover, in contrast to our findings in the patient`s cells only low levels of mutant transcript were found in the nucleus; a fraction of the transcript did appear in the cytoplasm which had spliced the mutant donor site correctly. Nuclear run-on experiments demonstrated equal levels of transcription from each transgene. Expression of another donor mutation known to cause in-frame exon skipping in OI type IV was accurately reproduced in the minigene in transfected 3T3 cells. Our experience suggests that either mechanism can lead to formation of a null allele possibly related to the type of splicing events surrounding the potential stop codons. Understanding the rules governing inactivation of a collagen RNA transcript may be important in designing a strategy to inactivate a dominate negative mutation associated with the more severe forms of OI.

  3. 双胞胎同患先天性成骨不全%Congenital Osteogenesis Imperfecta in Twins

    Institute of Scientific and Technical Information of China (English)

    孟智慧

    2006-01-01

    例1,女,4d,双胎之大,因四肢活动少4d入院。系G1P1,孕39周,无窒息史,生后发现四肢活动少,哭时仅右上肢活动,双下肢不动,吃奶尚好,哭声响亮。母孕期体健,非近亲婚配,家族中无类似病史。查体:足月儿外貌,呼吸平稳,前额宽,额骨前突,枕部颅骨软化,

  4. Isolated dentinogenesis imperfecta and dentin dysplasia: revision of the classification.

    Science.gov (United States)

    de La Dure-Molla, Muriel; Philippe Fournier, Benjamin; Berdal, Ariane

    2015-04-01

    Dentinogenesis imperfecta is an autosomal dominant disease characterized by severe hypomineralization of dentin and altered dentin structure. Dentin extra cellular matrix is composed of 90% of collagen type I and 10% of non-collagenous proteins among which dentin sialoprotein (DSP), dentin glycoprotein (DGP) and dentin phosphoprotein (DPP) are crucial in dentinogenesis. These proteins are encoded by a single gene: dentin sialophosphoprotein (DSPP) and undergo several post-translational modifications such as glycosylation and phosphorylation to contribute and to control mineralization. Human mutations of this DSPP gene are responsible for three isolated dentinal diseases classified by Shield in 1973: type II and III dentinogenesis imperfecta and type II dentin dysplasia. Shield classification was based on clinical phenotypes observed in patient. Genetics results show now that these three diseases are a severity variation of the same pathology. So this review aims to revise and to propose a new classification of the isolated forms of DI to simplify diagnosis for practitioners.

  5. Homozygous and compound heterozygous MMP20 mutations in amelogenesis imperfecta.

    Science.gov (United States)

    Gasse, B; Karayigit, E; Mathieu, E; Jung, S; Garret, A; Huckert, M; Morkmued, S; Schneider, C; Vidal, L; Hemmerlé, J; Sire, J-Y; Bloch-Zupan, A

    2013-07-01

    In this article, we focus on hypomaturation autosomal-recessive-type amelogenesis imperfecta (type IIA2) and describe 2 new causal Matrix metalloproteinase 20 (MMP20) mutations validated in two unrelated families: a missense mutation p.T130I at the expected homozygous state, and a compound heterozygous mutation having the same mutation combined with a nucleotide deletion, leading to a premature stop codon (p.N120fz*2). We characterized the enamel structure of the latter case using scanning electron microscopy analysis and microanalysis (Energy-dispersive X-ray Spectroscopy, EDX) and confirmed the hypomaturation-type amelogenesis imperfecta as identified in the clinical diagnosis. The mineralized content was slightly decreased, with magnesium substituting for calcium in the crystal structure. The anomalies affected enamel with minimal inter-rod enamel present and apatite crystals perpendicular to the enamel prisms, suggesting a possible new role for MMP20 in enamel formation.

  6. Multidisciplinary approach for a patient with dentinogenesis imperfecta and anterior trauma.

    Science.gov (United States)

    Roh, Won-Jong; Kang, Seung-Goo; Kim, Su-Jung

    2010-09-01

    Dentinogenesis imperfecta is an inherited dentinal dysplasia involving several risks for orthodontic treatment. This case report describes the multidisciplinary treatment of a 17-year-old girl whose Class II Division 1 malocclusion was complicated by dentinogenesis imperfecta type II and maxillary anterior trauma.

  7. All-ceramic restorations for complete-mouth rehabilitation in dentinogenesis imperfecta: a case report.

    Science.gov (United States)

    Moundouri-Andritsakis, Heleni; Kourtis, Stephanos G; Andritsakis, Demetrios P

    2002-10-01

    Prosthetic treatment of patients with dentinogenesis imperfecta is a challenge for the dental practitioner because numerous factors have to be considered. The use of all-ceramic restorations to rehabilitate the dentition of a young patient with dentinogenesis imperfecta is reported. Clinical and laboratory procedures are described.

  8. Amelogenesis Imperfecta - An account of Three Generations affected in a Family

    Directory of Open Access Journals (Sweden)

    G Sarat

    2004-01-01

    Full Text Available Amelogenesis Imperfecta is a hereditary condition affecting dental enamel without any systemic manifestation. This condition can be inherited as either Autosomal or X-linked. In this case report, we discuss with the help of Pedigree Analysis, an account of three generations in a family affected by Autosomal Dominant, Hypoplastic type of Amelogenesis Imperfecta.

  9. Minimally invasive rehabilitation of a patient with amelogenesis imperfecta

    OpenAIRE

    Büchi, Dominik; Fehmer, Vincent; Sailer, Irena; Wolleb, Karin; Jung, Ronald

    2014-01-01

    This case report describes a minimally invasive step-by-step approach to treat a patient with amelogenesis imperfecta. This is a genetic developmental disorder of the dental enamel, which clinically manifests as white and dark discolorations of the teeth. The clinical examination did not reveal the true depth of the staining. Therefore, a step-wise treatment approach was chosen. The first step consisted of a home bleaching procedure, which led to a slight improvement of the esthetic appearanc...

  10. Immediate Desensitization in Teeth Affected by Amelogenesis Imperfecta

    OpenAIRE

    Moreira,Rudá França; Figueiredo,Rossana Gomes; Oliveira,Henrique Eduardo de; Fonseca,Ana Christina Lamosa da; Miranda,Mauro Sayão de

    2016-01-01

    Abstract The aim of this paper was to describe a clinical case of immediate dental desensitization using a self-etch adhesive system in an adolescent patient diagnosed with amelogenesis imperfecta (AI). AI was associated with severe tooth sensitivity, treated by the application of a universal adhesive system for desensitization of the teeth affected by AI. Reduction of tooth sensitivity was assessed using a visual analog scale during all reevaluations. The technique was effective for reducing...

  11. Noninvasive esthetic treatment for hypomaturation amelogenesis imperfecta: a case report.

    Science.gov (United States)

    Nahsan, Flávia Pardo Salata; Silva, Luciana Mendonça da; Lima, Thiago Mendes de; Bertocco, Verônica Pereira de Lima; Chui, Fabíola Mendonça da Silva; Martins, Leandro de Moura

    2016-01-01

    Enamel alterations, such as amelogenesis imperfecta, can compromise the harmony of the smile and the patient's self-esteem and may cause tooth sensitivity. A simple and effective treatment approach uses the natural stratification of composite resins to mask deficient enamel formation and mimic the natural appearance of the substrate. The operative steps and principles for restorative success are described in this case report with 36-month follow-up.

  12. Early restorative rehabilitation of children and adolescents with amelogenesis imperfecta

    OpenAIRE

    Pousette Lundgren, Gunilla

    2015-01-01

    Amelogenesis imperfecta (AI) is a rare, genetically determined defect in enamel mineralization. Patients with (AI) can present with rapid tooth loss or fractures of enamel and dental sensitivity as well as alterations in enamel thickness, color, and shape. These factors may compromise esthetic appearance and masticatory function. Existing treatment recommendations suggest using resin composite restorations until adulthood, although such restorations have a limited longevity. The mai...

  13. Distraction osteogenesis with pivot plate in the treatment of scaphocephaly.

    Science.gov (United States)

    Nam, Seung Min; Kim, Yong Bae; Shin, Ho Seong; Park, Eun Soo; Jung, Sung Gyun

    2011-01-01

    In scaphocephaly, traditional distraction osteogenesis increases only the bitemporal width. We describe distraction osteogenesis with a pivot plate for scaphocephaly, which not only increases the bitemporal width but also decreases the anteroposterior length. Three patients with scaphocephaly were treated using distraction osteogenesis with a pivot plate between January 2005 and June 2006. These children underwent cranial reshaping by gradual distraction using an external distraction device and pivot plate. The distraction rate was 1 mm/d, and the latency period was 5 days. The follow-up period after distraction osteogenesis ranged from 16 to 24 months. No specific complications, such as accidental removal of the distraction devices, infection, or neurologic problems in any patient, occurred. The mean distraction was 45 mm. The mean cranial index was 73.6. Distraction osteogenesis for scaphocephaly is still in the development stage, but it is becoming accepted as a useful method because of its many advantages. Distraction osteogenesis with a pivot plate for scaphocephaly is better than other distraction osteogenesis techniques because it induces increased bitemporal width and decreased anteroposterior length synchronously.

  14. Maxillary Tuberosity Reconstruction with Transport Distraction Osteogenesis

    Directory of Open Access Journals (Sweden)

    F. Ugurlu

    2012-01-01

    Full Text Available Severe bone loss due to pathology in the maxillary tuberosity region is a challenging problem both surgically and prosthetically. Large bone grafts have a poor survival rate due to the delicate bony architecture in this area and presence of the maxillary sinus. Our case presentation describes a new technique for reconstructing severe bony defect in the maxillary tuberosity with horizontal distraction osteogenesis in a 45-year-old man. A 4×6×3cm cyst was discovered in the left maxillary molar region and enucleated. Three months postoperatively, the area had a severe bone defect extending to the zygomatic buttress superiorly and hamular notch posteriorly. Three months later, a bone segment including the right upper second premolar was osteotomised and distracted horizontally. The bone segment was distracted 15 mm distally. After consolidation, implants were placed when the distractor was removed. A fixed denture was loaded over the implants after 3 months. Complete alveolar bone loss extending to the cranial base can be reconstructed with transport distraction osteogenesis. Distalisation of the alveolar bone segment adjacent to the bony defect is an easy method for reconstructing such severe defects.

  15. Management of Mandibular Hypoplasia Using Distraction Osteogenesis Technique

    Institute of Scientific and Technical Information of China (English)

    陶学金; 樊敏; 凌翔; 陈卫民

    2004-01-01

    Summary: By using distraction osteogenesis technique, 3 cases of mandibular hypoplasia were treated by home-made and German-made jaw distractors: including one patient suffered from bilateral ankylosis of temporo-mandibular joint and 2 patients from deficiency of mandible. The duration of distraction osteogenesis was one month. The bone distractor was removed 3 months after operation. Satisfactory results were obtained in all 3 cases. Distraction osteogenesis can successfully be used in mandibular functional reconstruction and has much more advantages than traditional technique.

  16. [Distraction osteogenesis of deficient alveolar bone prior to dental rehabilitation].

    Science.gov (United States)

    Shilo, D; Emodi, O; Aizenbud, D; Rachmiel, A

    2015-07-01

    Implant supported rehabilitation has become very common in treatment plans nowadays, yet many patients lack the vertical and horizontal bone dimensions required for endosseous implant insertion. Distraction osteogenesis is a technique in which bone is generated by progressive elongation of two bone fragments following an osteotomy or corticotomy. Distraction osteogenesis of the alveolar ridge as a treatment modality in implant dentistry is a very useful technique that allows for adequate bone formation suitable for implant insertion. Alveolar distraction can be unidirectional, bidirectional, multidirectional or horizontal. Alveolar distraction osteogenesis can be performed by using intraosseous distraction devices, intraosseous distraction implants or by extraosseous devices which are the most prevalent today. Distraction osteogenesis has many advantages such as gradual lengthening of the bone with no need for an autogenous bone graft and lack of the associated donor site morbidity as well as distraction of the surrounding soft tissue together with the transported bone. One of the major challenges when using alveolar distraction osteogenesis is controlling the vector of distraction, this problem should be further addressed in future researches. We describe different methods for alveolar distraction osteogenesis, including the surgical procedure, latency period, lengthening and consolidation period. We also discuss the advantages, disadvantages and complications of the method. In this manuscript a case of mandibular alveolar deficiency following mandibular fracture and loss of teeth and the alveolar bone is presented. This patient was treated by alveolar distraction osteogenesis with excellent results. This patient was later rehabilitated . using endosseous implants as demonstrated by radiographs. Alveolar distraction osteogenesis provides a method to regain both hard tissue and soft tissue without additional grafting and is an efficient modality in cases of medium

  17. An isogenic model of murine mandibular distraction osteogenesis.

    Science.gov (United States)

    Deshpande, Sagar S; Weiss, Daniela M; Donneys, Alexis; Gallagher, Katherine K; Tchanque-Fossuo, Catherine N; Sarhaddi, Deniz; Buchman, Steven R

    2013-03-01

    The advent of stem cell-based therapies makes current models of mandibular distraction osteogenesis unwieldy. We thereby designed an isogenic model of distraction osteogenesis whose purpose was to allow for the free transfer of cells and components between rats. As immune response plays a significant role in healing and prevention of infection, an immune-competent mode is desirable rather than an athymic rat/xenograft model. The purposes of this study were as follows: (1) to replicate established models of distraction osteogenesis in a rodent model using an isogenic rat strain, and (2) to characterize the differences between inbred, isogenic rats and outbred rats in mandibular distraction osteogenesis via radiomorphometry and biomechanical response analysis. We demonstrated successful distraction osteogenesis to 5.1 mm in all Lewis (isogenic) rat mandibles as well as all Sprague-Dawley (outbred) rat mandibles, with no significant difference in volume-normalized radiomorphometrics, trending difference in non-volume-normalized radiomorphometrics and significant differences in biomechanical response parameters. We attribute the differences demonstrated to the decreased size of the Lewis rat mandible in comparison to Sprague-Dawley mandibles. We also provide information with caring with the additional needs of the Lewis rat. Given these differences, we find that Lewis rats function as an excellent model for isogenic mandibular distraction osteogenesis, but data procured may not be comparable between isogenic and nonisogenic models.

  18. Esthetic and functional rehabilitation of mutilated dentition and loss of vertical dimension due to amelogenesis imperfecta.

    Science.gov (United States)

    Mittal, Shweta; Tewari, Sanjay; Goel, Rajat

    2014-04-01

    Cases of severe attrition are a common finding. Among the congenital anomalies, amelogenesis imperfecta and dentinogenesis imperfecta are important conditions that may cause accelerated wear of teeth. The following case report describes the complete oral rehabilitation of a patient diagnosed with amelogenesis imperfecta. A detailed treatment plan was chalked out which included proper oral hygiene measures, restoration of carious teeth and endodontic treatment followed by foundation restorations of teeth that were crucial for the final prostheses. Patient was given transitional restorations for about 6 weeks with the aim of regaining the lost vertical dimensions. Final rehabilitation was done by fixed dental prostheses.

  19. Adhesive Restorations as An Esthetic Solution in Dentinogenesis Imperfecta.

    Science.gov (United States)

    Ubaldini, Adriana Lemos Mori; Giorgi, Maria Cecília Caldas; Carvalho, Ariany Borges; Pascon, Fernanda Miori; Lima, Débora Alves Nunes Leite; Baron, Gisele Maria Marchi; Paulillo, Luís Alexandre Maffei Sartini; Aguiar, Flávio Henrique Baggio

    2015-01-01

    Loss of tooth structure is the main sequela of dentinogenesis imperfecta (DI). Due to severe enamel attrition, patients with DI often present with esthetic, occlusal, endodontic, and speech complications. Therefore, an interdisciplinary approach, divided into separate clinical steps, should be developed to provide comprehensive dental rehabilitation. The purpose of this case report is to discuss the use of composite resin restorations as a transitional treatment step for the anterior teeth of an eight-year-old boy with DI until his bone and dental development permit orthodontic and orthognatic surgery.

  20. Management of dentinogenesis imperfecta: a review of two case reports.

    Science.gov (United States)

    Rafeek, Reisha N; Paryag, Amit; Al-Bayaty, Haytham

    2013-01-01

    Dentinogenesis imperfecta (DI) is an inherited disorder that affects dentin and often manifests as tooth discoloration; in addition, the dentition is also extremely susceptible to wear. Treatment of DI focuses primarily on protecting affected dentin, reducing sensitivity, and improving esthetics. Routine restorative materials, such as amalgams and composites, may be used. In more severe cases, the treatment of choice is full coverage crowns, while bonding of veneers may be used to improve the esthetics of the anterior teeth. This study presents two cases of Type II DI in the same family and the management of each case. Restorative management included amalgams, composite veneers, crowns, bridges, and overdentures.

  1. Crown lengthening procedure in the management of amelogenesis imperfecta

    Science.gov (United States)

    Kalaivani, S.; Manohar, Jenish; Shakunthala, P.; Sujatha, S.; Rajasekaran, S. A.; Karthikeyan, B.; Kalaiselvan, S.

    2015-01-01

    Full mouth rehabilitation includes a promising treatment planning and execution thus fulfilling esthetic, occlusal, and functional parameters maintaining the harmony of the stomatognathic system. Crown lengthening procedures have become an integral component of the esthetic armamentarium and are utilized with increasing frequency to enhance the appearance of restorations placed in the esthetic zone. Crown lengthening plays a role to create healthy relationship of the gingiva and bone levels so as to gain access to more of the tooth which can be restored, if it is badly worn, decayed or fractured, below the gum line. This paper highlights the full mouth crown lengthening procedure performed on a patient with amelogenesis imperfecta. PMID:26538965

  2. Dentinogenesis imperfecta type II: an affected family saga.

    Science.gov (United States)

    Kamboj, Mala; Chandra, Anil

    2007-09-01

    Dentinogenesis imperfecta (DI) type II or hereditary opalescent dentin is inherited in simple autosomal dominant mode with high penetrance and low mutation rate. It generally affects both the deciduous and permanent dentitions. DI type II corresponds to a localized form of mesodermal dysplasia, observed in histodifferentiation. Early diagnosis and treatment are therefore, fundamental, aiming at obtaining a favourable prognosis since late intervention makes treatment more complex. We present two cases of DI type II with the disease affecting three generations of a family in India, and briefly highlight the molecular basis of this disease.

  3. Crown lengthening procedure in the management of amelogenesis imperfecta.

    Science.gov (United States)

    Kalaivani, S; Manohar, Jenish; Shakunthala, P; Sujatha, S; Rajasekaran, S A; Karthikeyan, B; Kalaiselvan, S

    2015-08-01

    Full mouth rehabilitation includes a promising treatment planning and execution thus fulfilling esthetic, occlusal, and functional parameters maintaining the harmony of the stomatognathic system. Crown lengthening procedures have become an integral component of the esthetic armamentarium and are utilized with increasing frequency to enhance the appearance of restorations placed in the esthetic zone. Crown lengthening plays a role to create healthy relationship of the gingiva and bone levels so as to gain access to more of the tooth which can be restored, if it is badly worn, decayed or fractured, below the gum line. This paper highlights the full mouth crown lengthening procedure performed on a patient with amelogenesis imperfecta.

  4. Amelogenesis Imperfecta, Facial Esthetics and Snap-On Smile.

    Science.gov (United States)

    Wilson, Lee; Bradshaw, Jonathan P; Marks, Murray K

    2015-01-01

    Amelogenesis imperfecta is a hereditary enamel protein disorder affecting deciduous and secondary crown formation. The prevalence ranges from 1:700 to 1:14,000 depending on the population. These teeth may be hypoplastic, hypomineralized, or hypermineralized and are often discolored, sensitive and caries vulnerable. Patients often present with psychosocial issues due to appearance. Primary teeth are often treated with stainless steel crowns while secondary teeth are treated with full coverage esthetic crowns. The presenting preteen male here was fitted with Snap-On Smile? (www.snaponsmile.com). This treatment option provided cosmetic enhancement of the patient's appearance besides stabilization without altering the primary and secondary dentition during adolescent development.

  5. Amelogenesis imperfecta - lifelong management. Restorative management of the adult patient.

    Science.gov (United States)

    Patel, M; McDonnell, S T; Iram, S; Chan, M F W-Y

    2013-11-08

    The biggest challenge restorative dentists face in rehabilitating patients with amelogenesis imperfecta (AI) is trying to restore aesthetics, function and occlusal stability while keeping the treatment as conservative as possible. The goals of treatment should be to prolong the life of the patient's own teeth and avoid or delay the need for extractions and subsequent replacement with conventional fixed, removable or implant retained prostheses. In order to achieve these goals a stepwise approach to treatment planning is required starting with the most conservative but aesthetically acceptable treatment. This article discusses the management of AI and presents the various treatment options available for restoring the adult patient who presents to the dentist with AI.

  6. Immediate Desensitization in Teeth Affected by Amelogenesis Imperfecta.

    Science.gov (United States)

    Moreira, Rudá França; Figueiredo, Rossana Gomes; Oliveira, Henrique Eduardo; Fonseca, Ana Christina Lamosa da; Miranda, Mauro Sayão de

    2016-01-01

    The aim of this paper was to describe a clinical case of immediate dental desensitization using a self-etch adhesive system in an adolescent patient diagnosed with amelogenesis imperfecta (AI). AI was associated with severe tooth sensitivity, treated by the application of a universal adhesive system for desensitization of the teeth affected by AI. Reduction of tooth sensitivity was assessed using a visual analog scale during all reevaluations. The technique was effective for reducing tooth sensitivity. It was concluded that the adhesive system for tooth desensitization had an immediate effect and maintained its effectiveness during a 12-month follow-up period.

  7. Conservative treatment for amelogenesis imperfecta: a case report.

    Science.gov (United States)

    Campos, Roberto Elias; Miranda Valdivia, Andrea Dolores Correia; Santos-Filho, Paulo Cesar de Freitas; Menezes, Murilo de Souza; de Oliveira Junior, Osmir Batista; Soares, Carlos Jose

    2014-01-01

    Amelogenesis imperfecta is a hereditary condition that can alter the thickness, color, and shape of tooth enamel. Recent adhesive materials and techniques have provided less invasive treatment options. This case report presents the treatment of a patient whose anterior teeth had color alterations, white spots, pits, and shape defects. Using a more conservative technique, the mandibular and maxillary anterior teeth were restored using veneer direct composite restorations. After 6 years, the restorations demonstrated no deterioration, and no pathology was seen in association with the rehabilitation.

  8. [Dentinogenesis imperfecta: a developmental anomaly of the dentin in the primary dentition. A literature review].

    Science.gov (United States)

    Bercovich, R

    2010-01-01

    This literature review summarizes the current knowledge about Dentinigenesis Imperfecta, a developmental anomaly of thedentin.The phenomenon's classification is presented in details, as well as its etiology, clinical, rentgenological and histological characteristics. In addition, the treatment modes are described.

  9. LAMB3 mutations causing autosomal-dominant amelogenesis imperfecta.

    Science.gov (United States)

    Kim, J W; Seymen, F; Lee, K E; Ko, J; Yildirim, M; Tuna, E B; Gencay, K; Shin, T J; Kyun, H K; Simmer, J P; Hu, J C-C

    2013-10-01

    Amelogenesis imperfecta (AI) can be either isolated or part of a larger syndrome. Junctional epidermolysis bullosa (JEB) is a collection of autosomal-recessive disorders featuring AI associated with skin fragility and other symptoms. JEB is a recessive syndrome usually caused by mutations in both alleles of COL17A1, LAMA3, LAMB3, or LAMC2. In rare cases, heterozygous carriers in JEB kindreds display enamel malformations in the absence of skin fragility (isolated AI). We recruited two kindreds with autosomal-dominant amelogenesis imperfecta (ADAI) characterized by generalized severe enamel hypoplasia with deep linear grooves and pits. Whole-exome sequencing of both probands identified novel heterozygous mutations in the last exon of LAMB3 that likely truncated the protein. The mutations perfectly segregated with the enamel defects in both families. In Family 1, an 8-bp deletion (c.3446_3453del GACTGGAG) shifted the reading frame (p.Gly 1149Glufs*8). In Family 2, a single nucleotide substitution (c.C3431A) generated an in-frame translation termination codon (p.Ser1144*). We conclude that enamel formation is particularly sensitive to defects in hemidesmosome/basement-membrane complexes and that syndromic and non-syndromic forms of AI can be etiologically related.

  10. Occurrence of epidermolysis bullosa along with Amelogenesis imperfecta in female patient of India

    Directory of Open Access Journals (Sweden)

    A P Javed

    2013-01-01

    Full Text Available Epidermolysis bullosa (EB is an inherited disorder, which is characteristically presented as skin blisters developing in response to minor injury. Junctional variety of EB is also associated with enamel hypoplasia. Amelogenesis imperfecta presents with abnormal formation of the enamel both in deciduous and permanent dentition. This article describes a previously unreported case of Amelogenesis imperfecta with complete loss of enamel in a young female patient with EB.

  11. Occurrence of epidermolysis bullosa along with Amelogenesis imperfecta in female patient of India.

    Science.gov (United States)

    Javed, A P; Shenai, Prashanth; Chatra, Laxmikanth; Veena, K M; Rao, Prasanna Kumar; Prabhu, Rachana

    2013-11-01

    Epidermolysis bullosa (EB) is an inherited disorder, which is characteristically presented as skin blisters developing in response to minor injury. Junctional variety of EB is also associated with enamel hypoplasia. Amelogenesis imperfecta presents with abnormal formation of the enamel both in deciduous and permanent dentition. This article describes a previously unreported case of Amelogenesis imperfecta with complete loss of enamel in a young female patient with EB.

  12. The distraction osteogenesis in midfacial hypoplasia.

    Science.gov (United States)

    Lucchese, Alessandra; Gherlone, Enrico F; Asperio, Paolo; Baena, Ruggero Rodriguez y

    2014-05-01

    Distraction osteogenesis (DO) can generate new bone in a gap between 2 vascularized bone surfaces in response to application of graduated tensile stress across the bone gap. The authors present the clinical result in a cleft patient with severe maxillary deficiency treated by a rigid external distraction (RED) device. A boy complained of both masticatory and psychological problems because of cleft with severe midfacial retrusion. The treatment aimed to create a well-balanced facial profile, increase maxillary incisal display, create proper overjet and overbite, and align his dentition. By the RED system, the traction is applied to the maxilla through the dentition by an intraoral splint. A complete Le Fort I osteotomy was performed, including pterygomaxillary and septal disjunction, with mobilization. Once osteotomy was completed, the halo portion of the RED device was adjusted for the width of the neurocranium and was rigidly fixed around the head with 2 scalp screws on each side. A well-balanced facial profile and a good alignment of the dentition were obtained. The patients had considerable improvement in his self-esteem. Clinical reports have suggested that maxillary advancements achieved by distraction are more stable than those achieved with orthognathic surgery with a minimal influence on velopharyngeal competence.

  13. MicroRNAs regulate osteogenesis and chondrogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Shiwu, E-mail: shiwudong@gmail.com [Laboratory of Biomechanics, Department of Anatomy, The Third Military Medical University, Chongqing (China); Yang, Bo; Guo, Hongfeng; Kang, Fei [Laboratory of Biomechanics, Department of Anatomy, The Third Military Medical University, Chongqing (China)

    2012-02-24

    Highlights: Black-Right-Pointing-Pointer To focus on the role of miRNAs in chondrogenesis and osteogenesis. Black-Right-Pointing-Pointer Involved in the regulation of miRNAs in osteoarthritis. Black-Right-Pointing-Pointer To speculate some therapeutic targets for bone diseases. -- Abstract: MicroRNAs (miRNAs) are a class of small molecules and non-coding single strand RNAs that regulate gene expression at the post-transcriptional level by binding to specific sequences within target genes. miRNAs have been recognized as important regulatory factors in organism development and disease expression. Some miRNAs regulate the proliferation and differentiation of osteoblasts, osteoclasts and chondrocytes, eventually influencing metabolism and bone formation. miRNAs are expected to provide potential gene therapy targets for the clinical treatment of metabolic bone diseases and bone injuries. Here, we review the recent research progress on the regulation of miRNAs in bone biology, with a particular focus on the miRNA-mediated control mechanisms of bone and cartilage formation.

  14. Quantitative assessment of mineralization in distraction osteogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Hazra, Sunit; Biswal, Sandeep; Jang, Ki-Mo; Modi, Hitesh N. [Korea University, Guro Hospital, Department of Orthopedic Surgery, Seoul (Korea); Song, Hae-Ryong [Rare Diseases Institute, Korea University, Guro Hospital, Department of Orthopedic Surgery, Seoul (Korea); Lee, Suk-Ha [Konkuk University Hospital, Department of Orthopedics, Seoul (Korea); Lee, Seok Hyun [Dongguk University International Hospital, Department of Orthopedic Surgery, Ilsan (Korea)

    2008-09-15

    The most important decision in distraction osteogenesis is the timing of fixator removal. Various methods have been tried, such as radiographic appearance of callus and bone mineral density (BMD) assessment, but none has acquired gold standard status. The purpose of this study was to develop another objective method of assessment of callus stiffness to help clinicians in taking the most important decision of when to remove the fixator. We made a retrospective study of 70 patients to compare the BMD ratio and pixel value ratio. These ratios were calculated at the time of fixator removal, and Pearson's coefficient of correlation was used to show the comparability. Inter- and intra-observer variability of the new method was also tested. Good correlation was found between BMD ratio and pixel value ratio, with a Pearson's coefficient of correlation of 0.79. The interobserver variability was also low, with high intra-observer reproducibility, suggesting that this test was simple to perform. Pixel value ratio is a good method for assessing callus stiffness, and it can be used to judge the timing of fixator removal. (orig.)

  15. Trifocal distraction osteogenesis for reconstruction of skull defect

    Institute of Scientific and Technical Information of China (English)

    Ke Ke; Hai-Song Xu; Zhi-Hong Fan

    2013-01-01

    Objective:To apply trifocal distraction osteogenesis in canine model of skull segmental defects and to provide reference for clinical treatment. Methods:Six labrador dogs were selected in this study and divided into observation group and control group randomly. Each group contained 3 dogs. Skull segmental defects models were established by surgery, and dogs in bservation group received trifocal distraction osteogenesis treatment. Bone density was observed and compared between two groups during treatment. Results: There were no significant difference in bone density between two groups on th 1st day (P>0.05). The bone density of observation group on the 30th day, and 60th day were higher than that of control group (P<0.01). Conclusions: Trifocal distraction osteogenesis has significant clinical effect, and it would be widely used in clinical treatment.

  16. Le fort I maxillary advancement using distraction osteogenesis.

    Science.gov (United States)

    Combs, Patrick D; Harshbarger, Raymond J

    2014-11-01

    Treatment of maxillary hypoplasia has traditionally involved conventional Le Fort I osteotomies and advancement. Advancements of greater than 10 mm risk significant relapse. This risk is greater in the cleft lip and palate population, whose anatomy and soft tissue scarring from prior procedures contributes to instability of conventional maxillary advancement. Le Fort I advancement with distraction osteogenesis has emerged as viable, stable treatment modality correction of severe maxillary hypoplasia in cleft, syndromic, and noncleft patients. In this article, the authors provide a review of current data and recommendations concerning Le Fort I advancement with distraction osteogenesis. In addition, they outline their technique for treating severe maxillary hypoplasia with distraction osteogenesis using internal devices.

  17. Dental rehabilitation of amelogenesis imperfecta using thermoformed templates.

    Science.gov (United States)

    Sockalingam, Snmp

    2011-01-01

    Amelogenesis imperfecta represents a group of dental developmental conditions that are genomic in origin. Hypoplastic AI, hypomineralised AI or both in combination were the most common types seen clinically. This paper describes oral rehabilitation of a 9-year-old Malay girl with inherited hypoplastic AI using transparent thermoforming templates. The defective surface areas were reconstructed to their original dimensions on stone cast models of the upper and lower arches using composite, and transparent thermoform templates were fabricated on the models. The templates were used as crown formers to reconstruct the defective teeth clinically using esthetically matching composite. The usage of the templates allowed direct light curing of the composite, accurate reproducibility of the anatomic contours of the defective teeth, reduced chair-side time and easy contouring and placement of homogenous thickness of composite in otherwise inaccessible sites of the affected teeth.

  18. Dentinogenesis imperfecta type II: ultrastructure of teeth in sagittal sections.

    Science.gov (United States)

    Wieczorek, Aneta; Loster, Jolanta

    2013-01-01

    The morphological abnormalities of the teeth of patients affected by dentinogenesis imperfecta type 2 (DI-II) may underlie the difficulties with the clinical restoration of such teeth. We therefore performed a scanning electron microscopy (SEM) study of four permanent first mandibular molars of four DI-II patients with periapical pathosis. The teeth were prepared for SEM evaluation by standard methods. In the crown, the enamel presented a highly irregular surface with a number of cracks and crevices. In some places, only granular remains of the enamel were found, while in other parts of the crown, the enamel was absent. SEM examination revealed the structural changes responsible for the lower enamel's hardness and resistance to attrition, and for tooth wear, while the structural changes in the dentin may explain the failure of some adhesive restorative materials. This SEM study thus revealed structural defects which underlie the problems of attrition and restoration loss found in patients with this genetic dental condition.

  19. Multiple teeth fractures in dentinogenesis imperfecta: a case report.

    Science.gov (United States)

    Min, Boram; Song, Je Seon; Lee, Jae-Ho; Choi, Byung-Jai; Kim, Kwang-Mahn; Kim, Seong-Oh

    2014-01-01

    Dentinogenesis imperfecta (DGI) is a hereditary defect consisting of opalescent teeth composed of irregularly formed and hypomineralized dentin. This paper presents the multiple fractures of DGI-affected teeth and suggests the reason of low fracture resistance by observing the dentin microstructures directly using scanning electron microscope (SEM) and by measuring its surface hardness using the Vickers hardness test. SEM revealed that while the enamel microstructure was similar in the DGI-affected and normal teeth, the microstructure of the DGI-affected dentin was poorly woven and more loosely packed than that of the normal dentin. The Vickers hardness of the DGI-affected dentin was 4.89 times softer than the normal dentin. The low fracture resistance of DGI-affected teeth can be attributed to the poorly woven microstructure of their dentin, which leads to a reduction in hardness.

  20. Overlapping DSPP mutations cause dentin dysplasia and dentinogenesis imperfecta.

    Science.gov (United States)

    McKnight, D A; Simmer, J P; Hart, P S; Hart, T C; Fisher, L W

    2008-12-01

    Dentinogenesis imperfecta (DGI) and dentin dysplasia (DD) are allelic disorders due to mutations in DSPP. Typically, the phenotype breeds true within a family. Recently, two reports showed that 3 different net -1 bp frameshift mutations early in DSPP's repeat domain caused DD, whereas 6 more 3' frameshift mutations were associated with DGI. Here we identify a DD kindred with a novel -1 bp frameshift (c.3141delC) that falls within the portion of the DSPP repeat domain previously associated solely with the DGI phenotype. This new frameshift mutation shows that overlapping DSPP mutations can give rise to either DGI or DD phenotypes. Furthermore, the consistent kindred presentation of the DD or DGI phenotype appears to be dependent on an as-yet-undescribed genetic modifier closely linked to DSPP.

  1. Bilateral nephrocalcinosis and amelogenesis imperfecta: A case report

    Directory of Open Access Journals (Sweden)

    Alok Patel

    2015-01-01

    Full Text Available Amelogenesis imperfecta (AI is a group of hereditary disorders that affect the quality and/or quantity of dental enamel. This paper describes the clinicopathological features of a patient who was born of nonconsanguineous parents and who presented with oral alterations, including yellow and misshapen teeth, intrapulpal calcifications, delayed tooth eruption, and gum enlargement. Scanning electron microscopy of the teeth revealed hypoplastic enamel, and a renal ultrasound detected bilateral nephrocalcinosis, leading to a diagnosis of AI and nephrocalcinosis syndrome. Since nephrocalcinosis is often asymptomatic and can be associated with impaired renal function, dentists who see children with a generalized and thin hypoplastic AI should consider a renal ultrasound scan and referral to a Nephrologist. Children with nephrocalcinosis should also be considered for a dental check.

  2. Amelogenesis imperfecta: Report of a case and review of literature

    Directory of Open Access Journals (Sweden)

    Chaudhary Mayur

    2009-01-01

    Full Text Available Amelogenesis imperfecta (AI is a diverse collection of inherited diseases that exhibit quantitative or qualitative tooth enamel defects in the absence of systemic manifestations. Also known by varied names such as Hereditary enamel dysplasia, Hereditary brown enamel, Hereditary brown opalescent teeth, this defect is entirely ectodermal, since mesodermal components of the teeth are basically normal. The AI trait can be transmitted by either autosomal dominant, autosomal recessive, or X-linked modes of inheritance. Genes implicated in autosomal forms are genes encoding enamel matrix proteins, namely: enamelin and ameloblastin, tuftelin, MMP-20 and kallikrein - 4. This article presents a case reported to Dr. D. Y. Patil, Dental College and Hospital, Pune, India, along with a review of this often seen clinical entity.

  3. Amelogenesis Imperfecta and Screening of Mutation in Amelogenin Gene

    Directory of Open Access Journals (Sweden)

    Fernanda Veronese Oliveira

    2014-01-01

    Full Text Available The aim of this study was to report the clinical findings and the screening of mutations of amelogenin gene of a 7-year-old boy with amelogenesis imperfecta (AI. The genomic DNA was extracted from saliva of patient and his family, followed by PCR and direct DNA sequencing. The c.261C>T mutation was found in samples of mother, father, and brother, but the mutation was not found in the sequence of the patient. This mutation is a silent mutation and a single-nucleotide polymorphism (rs2106416. Thus, it is suggested that the mutation found was not related to the clinical presence of AI. Further research is necessary to examine larger number of patients and genes related to AI.

  4. Dental rehabilitation of amelogenesis imperfecta using thermoformed templates

    Directory of Open Access Journals (Sweden)

    SNMP Sockalingam

    2011-01-01

    Full Text Available Amelogenesis imperfecta represents a group of dental developmental conditions that are genomic in origin. Hypoplastic AI, hypomineralised AI or both in combination were the most common types seen clinically. This paper describes oral rehabilitation of a 9-year-old Malay girl with inherited hypoplastic AI using transparent thermoforming templates. The defective surface areas were reconstructed to their original dimensions on stone cast models of the upper and lower arches using composite, and transparent thermoform templates were fabricated on the models. The templates were used as crown formers to reconstruct the defective teeth clinically using esthetically matching composite. The usage of the templates allowed direct light curing of the composite, accurate reproducibility of the anatomic contours of the defective teeth, reduced chair-side time and easy contouring and placement of homogenous thickness of composite in otherwise inaccessible sites of the affected teeth.

  5. Amelogenesis imperfecta: A challenge to restoring esthetics and function

    Directory of Open Access Journals (Sweden)

    Ranganath V

    2010-01-01

    Full Text Available Rehabilitation of complicated cases poses difficulty in clinical practice, both with respect to restoring function and with esthetics. One such clinical condition where the dentist has to give importance to proper planning of the treatment and execution of the plan is amelogenesis imperfecta (AI, a condition where both function and esthetics are accommodated. This article discusses both the functional and esthetic rehabilitation of a patient with AI. Both the esthetics and function were hampered in this patient due to the condition. As a result, the treatment was properly planned and executed. A number of treatment options are available for us today to treat such a case. There is no one technique to be followed as such. However, the aim was to properly diagnose the case and provide good function and esthetics to the patient.

  6. Functional and esthetic rehabilitation of a patient with amelogenesis imperfecta.

    Science.gov (United States)

    Ergun, Gulfem; Kaya, Bekir Murat; Egilmez, Ferhan; Cekic-Nagas, Isil

    2013-01-01

    Amelogenesis imperfecta (AI) is a hereditary disorder that causes developmental alterations in the structure of enamel. In addition, tooth sensitivity, missing or impacted teeth, taurodontism, altered dental esthetics and anterior open bite can also be associated with AI. This clinical report presents the diagnosis, treatment planning and prosthetic rehabilitation of a 19-year-old female patient with AI associated with a group of dental anomalies. Following clinical and radiographic examination, histologic evaluation of the teeth confirmed the diagnosis of rough pattern hypoplastic AI. The patient was rehabilitated with full-mouth zirconium oxide ceramic fixed bridges. Adaptation of the temporomandibular joints and masticatory muscles to the bridges was carefully observed over 3 years. At the end of this follow-up period, the patient was satisfied with the esthetics, function and phonation of her prostheses.

  7. Bilateral nephrocalcinosis and amelogenesis imperfecta: A case report.

    Science.gov (United States)

    Patel, Alok; Jagtap, Chetana; Bhat, Chetan; Shah, Rohan

    2015-01-01

    Amelogenesis imperfecta (AI) is a group of hereditary disorders that affect the quality and/or quantity of dental enamel. This paper describes the clinicopathological features of a patient who was born of nonconsanguineous parents and who presented with oral alterations, including yellow and misshapen teeth, intrapulpal calcifications, delayed tooth eruption, and gum enlargement. Scanning electron microscopy of the teeth revealed hypoplastic enamel, and a renal ultrasound detected bilateral nephrocalcinosis, leading to a diagnosis of AI and nephrocalcinosis syndrome. Since nephrocalcinosis is often asymptomatic and can be associated with impaired renal function, dentists who see children with a generalized and thin hypoplastic AI should consider a renal ultrasound scan and referral to a Nephrologist. Children with nephrocalcinosis should also be considered for a dental check.

  8. Analysis and Literature Review of Osteogenesis Imperfect in A Family%成骨不全家系分析并文献复习

    Institute of Scientific and Technical Information of China (English)

    郑峰

    2012-01-01

    Osteogenesis Imperfecta ( OI) is a kind of autosomal dominant or recessive hereditary connective tissue disease and its clinical features are bone fragility and bone deformities. It is very rare in clinic. According to the main clinical symptoms and radiographic results, we found a pedigree with OI. The research in genetics and cytology being more and more thorough, the authors took this pedigree as the foundation and discussed its pathogenesis, diagnosis, treatment and rehabilitation problems. In addition, the relevant literature was reviewed as well.%成骨不全症是以骨脆弱和骨畸形为临床特征的常染色体显性或隐性遗传缺陷的结缔组织病,临床罕见,根据主要临床表现和影像学结果来确诊.现发现成骨不全症家系一例,面对基因学和细胞学正在不断深入的研究,笔者以此家系为基础,对其发病机制、诊断、治疗及康复等问题予以阐述并文献复习.

  9. Distraction osteogenesis in the irradiated mandible. A case report

    NARCIS (Netherlands)

    Raghoebar, GM; Jansma, J; Vissink, A; Roodenburg, JLN

    2005-01-01

    Background: Distraction osteogenesis has been suggested as a relatively simple method of mandibular reconstruction following ablative head and neck surgery. Some authors report good results in irradiated patients while other authors report limitations with this group of patients. Patient: In a 72-ye

  10. Upper airway outcomes following midface distraction osteogenesis: a systematic review.

    Science.gov (United States)

    Taylor, B A; Brace, M; Hong, P

    2014-07-01

    The objective of this paper is to systematically review the airway outcomes following distraction osteogenesis of midface with the goal of (1) deriving clinically oriented insights and (2) identifying gaps in knowledge to stimulate future research. Medline, EMBASE and Cochrane databases were searched and studies were included if subjects of any age had midface retrusion/hypoplasia and underwent midface distraction osteogenesis. Outcome measures of interest were any respiratory or airway associated measures, and reports of adverse events. A total of 368 abstracts were generated from the literature searches; 16 studies met the criteria for data extraction and analysis. All 16 studies were observational. Generally, midface distraction osteogenesis was reported to improve respiratory status and was well tolerated. Specifically, favorable outcomes in cephalometry (9 studies), polysomnography (9 studies), and decannulation rates (8 studies) were reported. In conclusion, upper airway status was improved in most patients who underwent midface distraction osteogenesis, yet long-term results and consistent objective measures are lacking. Studies reviewed were retrospective case series and details regarding patients who did not improve were deficient. A standardized prospective multicenter cohort trial with long-term patient follow up is required.

  11. Backward distraction osteogenesis in a patient with severe mandibular micrognathia.

    Science.gov (United States)

    Mitsukawa, Nobuyuki; Morishita, Tadashi; Saiga, Atsuomi; Akita, Shinsuke; Kubota, Yoshitaka; Satoh, Kaneshige

    2013-09-01

    Maxillary skeletal prognathism can involve severe mandibular micrognathia with marked mandibular retrognathism or hypoplasia. For patients with such a condition, a conventional treatment is mandibular advancement by sagittal split ramus osteotomy (SSRO). This procedure has problems such as insufficient advancement, instability of jaw position, and postoperative relapse. Thus, in recent years, mandibular distraction osteogenesis has been used in some patients. Mandibular distraction has many advantages, but an ideal occlusion is difficult to achieve using this procedure. That is, 3-dimensional control cannot be attained using an internal device that is unidirectional. This report describes a case of severe mandibular micrognathia in a 14-year-old girl treated using backward distraction osteogenesis. This procedure was first reported by Ishii et al (Jpn J Jaw Deform 2004; 14:49) and involves a combination of SSRO and ramus distraction osteogenesis. In the present study, intermaxillary fixation in centric occlusion was performed after osteotomy, and proximal bone segments were distracted in a posterosuperior direction. This procedure is a superior surgical technique that avoids the drawbacks of SSRO and conventional mandibular distraction. However, it applies a large load to the temporomandibular joints and requires thorough management. Thus, careful evaluation needs to be made of the indication for backward distraction osteogenesis.

  12. Complications in alveolar distraction osteogenesis of the atrophic mandible.

    NARCIS (Netherlands)

    Perdijk, F.B.; Meijer, G.J.; Strijen, P.J.; Koole, R.

    2007-01-01

    To improve the starting point for placement of dental implants, 45 patients suffering from atrophied edentulous mandibles, with a vertical height varying between 7.3 and 15.8mm, were treated by alveolar vertical distraction osteogenesis (VDO). The mean follow-up period was 3 years, ranging from 1 to

  13. Complications in alveolar distraction osteogenesis of the atrophic mandible

    NARCIS (Netherlands)

    Perdijk, F. B. T.; van Strijen, P. J.; Meijer, G.

    2007-01-01

    To improve the starting point for placement of dental implants, 45 patients suffering from atrophied edentulous mandibles, with a vertical height varying between 7.3 and 15.8 turn, were treated by alveolar vertical distraction osteogenesis (VDO). The mean follow-up period was 3 years, ranging from 1

  14. ECM remodelling components regulated during jaw periosteal cell osteogenesis.

    Science.gov (United States)

    Alexander, Dorothea; Ardjomandi, Nina; Munz, Adelheid; Friedrich, Björn; Reinert, Siegmar

    2011-10-01

    Human JPCs (jaw periosteal cells) are a promising source for the engineering of cell-based osteoinductive grafts in oral surgery. For this purpose, cell characteristics of this stem cell source should be elucidated in detail. Analysis of gene expression profiles may help us to evaluate key factors and cellular targets of JPC osteogenesis. Because little is known about the interplay of osteogenic-related components, we analysed the expression of different collagen types reflecting important players for extracellular matrix assembly and of TIMPs (tissue inhibitors of metalloproteinases) responsible for the inhibition of matrix degradation. Gene expression analyses using microarrays and quantitative RT-PCR (reverse transcription-PCR) during JPC osteogenesis revealed the induction of several collagen types' expression (VII, VIII, XI and XII), and some of them (types I, VIII and XI) seemed to be susceptible to BMP-2 (bone morphogenetic protein-2) that is known to be a potent osteogenic inducer of periosteal cells. Among the TIMPs, only TIMP-4 and RECK (reversion-inducing cysteine-rich protein with Kazal motifs) expressions were strongly up-regulated during JPC osteogenesis. Proteome profiler analysis of supernatants from untreated and differentiated JPCs confirmed the gene expression data in terms of TIMP expression. In summary, we identified new collagen types and TIMPs that seem to play important roles during the osteogenesis of jaw periosteal progenitor cells.

  15. Enamel renal syndrome with associated amelogenesis imperfecta, nephrolithiasis, and hypocitraturia: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Bhesania, Dhvani; Arora, Ankit; Kapoor, Sonali [Dept. of Conservative Dentistry and Endodontics, Manubhai Patel Dental College, Maharaja Krishnakumarsinhji Bhavnagar University, Vadodara (India)

    2015-09-15

    Numerous cases of enamel renal syndrome have been previously reported. Various terms, such as enamel renal syndrome, amelogenesis imperfecta and gingival fibromatosis syndrome, and enamel-renal-gingival syndrome, have been used for patients presenting with the dental phenotype characteristic of this condition, nephrocalcinosis or nephrolithiasis, and gingival findings. This report describes a case of amelogenesis imperfecta of the enamel agenesis variety with nephrolithiasis in a 21-year-old male patient who complained of small teeth. The imaging modalities employed were conventional radiography, cone-beam computed tomography, and renal sonography. Such cases are first encountered by dentists, as other organ or metabolic diseases are generally hidden. Hence, cases of amelogenesis imperfecta should be subjected to advanced diagnostic modalities, incorporating both dental and medical criteria, in order to facilitate comprehensive long-term management.

  16. Exonal deletion of SLC24A4 causes hypomaturation amelogenesis imperfecta.

    Science.gov (United States)

    Seymen, F; Lee, K-E; Tran Le, C G; Yildirim, M; Gencay, K; Lee, Z H; Kim, J-W

    2014-04-01

    Amelogenesis imperfecta is a heterogeneous group of genetic conditions affecting enamel formation. Recently, mutations in solute carrier family 24 member 4 (SLC24A4) have been identified to cause autosomal recessive hypomaturation amelogenesis imperfecta. We recruited a consanguineous family with hypomaturation amelogenesis imperfecta with generalized brown discoloration. Sequencing of the candidate genes identified a 10-kb deletion, including exons 15, 16, and most of the last exon of the SLC24A4 gene. Interestingly, this deletion was caused by homologous recombination between two 354-bp-long homologous sequences located in intron 14 and the 3' UTR. This is the first report of exonal deletion in SLC24A4 providing confirmatory evidence that the function of SLC24A4 in calcium transport has a crucial role in the maturation stage of amelogenesis.

  17. Amelogenesis Imperfecta with Taurodontism, Microdontia, and Minor Thalassemia: A Case Report

    Directory of Open Access Journals (Sweden)

    Fatemeh Mazhari

    2013-12-01

    Full Text Available Amelogenesis imperfecta is a group of genetic disorders that affects both the morphology and quality of tooth structure. Although the disease entity is primarily associated with abnormalities of dental and oral structures, it has been reported to be associated with a few syndromes. A 9-year-old girl with minor thalassemia referred to the Department of Pediatric Dentistry of the Mashhad Faculty of Dentistry with a complaint of sensitivity of first permanent molars. Dental findings consisted of amelogenesis imperfecta, microdontia, posterior cross bite and taurodontism. This is the first report of thalassemia accompanied with amelogenesis imperfecta. Although the patients often are non-symptomatic, the trait can be passed on to a child and if both parents carry the trait, the child could develop a more severe form of the disease; therefore, early diagnosis is important.

  18. Enamel renal syndrome with associated amelogenesis imperfecta, nephrolithiasis, and hypocitraturia: A case report.

    Science.gov (United States)

    Bhesania, Dhvani; Arora, Ankit; Kapoor, Sonali

    2015-09-01

    Numerous cases of enamel renal syndrome have been previously reported. Various terms, such as enamel renal syndrome, amelogenesis imperfecta and gingival fibromatosis syndrome, and enamel-renal-gingival syndrome, have been used for patients presenting with the dental phenotype characteristic of this condition, nephrocalcinosis or nephrolithiasis, and gingival findings. This report describes a case of amelogenesis imperfecta of the enamel agenesis variety with nephrolithiasis in a 21-year-old male patient who complained of small teeth. The imaging modalities employed were conventional radiography, cone-beam computed tomography, and renal sonography. Such cases are first encountered by dentists, as other organ or metabolic diseases are generally hidden. Hence, cases of amelogenesis imperfecta should be subjected to advanced diagnostic modalities, incorporating both dental and medical criteria, in order to facilitate comprehensive long-term management.

  19. Vertebral Compression Fractures

    Science.gov (United States)

    ... www.oif.org Email: bonelink@oif.org The Osteogenesis Imperfecta Foundation, Inc. is the only voluntary national health ... helping people cope with the problems associated with osteogenesis imperfecta. The Foundation's mission is to improve the quality ...

  20. Transition from Pediatric to Adult OI Care

    Science.gov (United States)

    ... www.oif.org Email: bonelink@oif.org The Osteogenesis Imperfecta Foundation, Inc. is the only voluntary national health ... helping people cope with the problems associated with osteogenesis imperfecta. The Foundation's mission is to improve the quality ...

  1. Hypophosphatasia

    Science.gov (United States)

    ... www.oif.org Email: bonelink@oif.org The Osteogenesis Imperfecta Foundation, Inc. is the only voluntary national health ... helping people cope with the problems associated with osteogenesis imperfecta. The Foundation's mission is to improve the quality ...

  2. Surgery Considerations for Adults and Children

    Science.gov (United States)

    ... www.oif.org Email: bonelink@oif.org The Osteogenesis Imperfecta Foundation, Inc. is the only voluntary national health ... helping people cope with the problems associated with osteogenesis imperfecta. The Foundation's mission is to improve the quality ...

  3. Fracture Management

    Science.gov (United States)

    ... www.oif.org Email: bonelink@oif.org The Osteogenesis Imperfecta Foundation, Inc. is the only voluntary national health ... helping people cope with the problems associated with osteogenesis imperfecta. The Foundation's mission is to improve the quality ...

  4. Diagnosis and esthetic functional rehabilitation of a patient with amelogenesis imperfecta.

    Science.gov (United States)

    Oliveira, Ilione Kruschewsky Costa Sousa; Fonseca, Jussara de Fatima Barbosa; do Amaral, Flavia Lucisano Botelho; Pecorari, Vanessa Gallego Arias; Basting, Roberta Tarkany; França, Fabiana Mantovani Gomes

    2011-06-01

    Amelogenesis imperfecta is a hereditary disease that causes structural anomalies in dental enamel of both the primary and permanent dentition. The anomaly may present a variety of clinical forms and appearances, with its main characteristics being the loss of tooth structure, compromised esthetic appearance, and dental sensitivity. The aim of this study was to present the clinical report of a 16-year-old patient with severely compromised esthetics as a result of amelogenesis imperfecta of the hypocalcified type who was rehabilitated with composite resin and ceramic crowns.

  5. Dentinogenesis imperfecta - hardness and Young's modulus of teeth.

    Science.gov (United States)

    Wieczorek, Aneta; Loster, Jolanta; Ryniewicz, Wojciech; Ryniewicz, Anna M

    2013-01-01

    Dentinogenesis imperfecta type II (DI-II) is the most common dental genetic disease with reported incidence 1 in 8000. Elasticity and hardness of the enamel of teeth are important values which are connected with their resistance to attrition. It is hypothesized that values of physical properties for healthy teeth and teeth with DI-II are different. The aim of the study was to investigate some physical properties of teeth extracted from patients with DI-II in comparison with normal teeth. The material of the study was six teeth: three lower molars, with clinical signs of DI-II, which were extracted due to complications of pulp inflammation and three other lower molars which were extracted for orthodontic reasons - well formed, without any signs of pathology. The surfaces of DI-II and normal teeth were tested on the CSM Instruments Scratch Tester machine (producer CSEM Switzerland) by Oliver and Pharr method. The indenter used was Vicker's VG-73 diamond indenter. Additionally, the Scanning Electron Microscopy (SEM) analysis of the surface of the teeth with DI-II was made. Vickers hardness of the teeth with dental pathology (DI-II) was seven times smaller, and Young's modulus six times smaller than those of healthy teeth. The parameters of hardness and elasticity of enamel of teeth with clinical diagnosis of DI-II were very much smaller than in normal teeth and because of that can be responsible for attrition.

  6. Novel dentin phosphoprotein frameshift mutations in dentinogenesis imperfecta type II.

    Science.gov (United States)

    Lee, K-E; Kang, H-Y; Lee, S-K; Yoo, S-H; Lee, J-C; Hwang, Y-H; Nam, K H; Kim, J-S; Park, J-C; Kim, J-W

    2011-04-01

    The dentin sialophosphoprotein (DSPP) gene encodes the most abundant non-collagenous protein in tooth dentin and DSPP protein is cleaved into several segments including the highly phosphorylated dentin phosphoprotein (DPP). Mutations in the DSPP gene have been solely related to non-syndromic form of hereditary dentin defects. We recruited three Korean families with dentinogenesis imperfecta (DGI) type II and sequenced the exons and exon-intron boundaries of the DSPP gene based on the candidate gene approach. Direct sequencing of PCR products and allele-specific cloning of the highly repetitive exon 5 revealed novel single base pair (bp) deletional mutations (c.2688delT and c.3560delG) introducing hydrophobic amino acids in the hydrophilic repeat domain of the DPP coding region. All affected members of the three families showed exceptionally rapid pulp chambers obliteration, even before tooth eruption. Individuals with the c.3560delG mutation showed only mild, yellowish tooth discoloration, in contrast to the affected individuals from two families with c.2688delT mutation. We believe that these results will help us to understand the molecular pathogenesis of DGI type II as well as the normal process of dentin biomineralization.

  7. Prosthetic treatment in dentinogenesis imperfecta type II: a case report

    Directory of Open Access Journals (Sweden)

    Sedat Güven

    2016-05-01

    Full Text Available INTRODUCTION: Dentinogenesis imperfecta (DI or hereditary opalescent dentin is an autosomal dominant disorder affecting both primary and permanent dentition. Early diagnosis and treatment of DI is important for normal facial growth and esthetic continuity by preserving occlusion and tooth structure. It also provides psychological motivation by increasing the patient’s quality of life. Providing functional dentition in DI patients prevents loss of the vertical dimension, while enabling normal growth of the facial bones and jaw joint. CASE REPORT: A 20-year-old male with DI was referred to our clinic with chewing difficulty and esthetic and speech problems. His brother also had this disease. Oral examination showed the loss of many teeth and the absence of enamel on most of the remaining teeth, causing discoloration and exposing soft dentinal tissue with calcification disorder. Despite widespread attrition of the teeth, pulp chambers were not exposed. The tip of the lower jaw was prominent in the patient’s profile. Placing metal-ceramic fixed dentures in the lower jaw and an overdenture prosthesis in the upper jaw improved the patient’s psychological state as well as his function, phonation, and esthetics. CONCLUSION: This case report presents the intraoral findings in a patient with DI, including the histopathological findings, and the prosthetic treatment approach and the treatment outcome.

  8. Dentinogenesis imperfecta type II: approach for dental treatment

    Directory of Open Access Journals (Sweden)

    Raquel Mantuaneli Scarel-Caminaga

    Full Text Available INTRODUCTION: Dentinogenesis imperfecta (DI is a hereditary dentin development disorder that affects both primary and permanent dentitions. The DI characteristics are discolored and translucent teeth ranging from gray to brownish-blue or amber. The enamel may split readily from the dentin when subjected to occlusal stress. Radiographically there are evident of cervical constrictions, short root and pulp chambers, and the root canals are smaller than normal or completely obliterated. The dental treatment choice can be decided on a case-by case‑basis, considering the degree of dental tissue loss, and child age and cooperation. OBJECTIVE: The aim of this case report was to describe the early dental treatment performed in a child affected by DI type II. CASE REPORT: The treatment involved basic preventive procedures. Primary molars were worn to such an extent that the remained tooth structure was covered with composite resin to protect the exposed dentin. Resin-based sealant was applied in all first permanent molars. Posterior cross bite was treated with the expansion of the upper arch. CONCLUSION: The early treatment restored the patient´s vertical dimension resulting in acceptable esthetics and function for the permanent teeth to complete their eruption.

  9. Genetic mapping of the dentinogenesis imperfecta type II locus

    Energy Technology Data Exchange (ETDEWEB)

    Crosby, A.H.; Dixon, M.J. [Univ. of Manchester (United Kingdom); Scherpbier-Heddema, T. [Fox Chase Cancer Center, Philadelphia, PA (United States)] [and others

    1995-10-01

    Dentinogenesis imperfecta type II (DGI-II) is an autosomal dominant disorder of dentin formation, which has previously been mapped to chromosome 4q12-21. In the current study, six novel short tandem-repeat polymorphisms (STRPs) have been isolated, five of which show significant evidence of linkage to DGI-II. To determine the order of the STRPs and define the genetic distance between them, nine loci (including polymorphisms for two known genes) were mapped through the CEPH reference pedigrees. The resulting genetic map encompasses 16.3 cM on the sex-averaged map. To combine this map with a physical map of the region, all of the STRPs were mapped through a somatic cell hybrid panel. The most likely location for the DGI-II locus within the fixed marker map is in the D4S2691-D4S2692 interval of 6.6 cM. The presence of a marker that shows no recombination with the DGI-II phenotype between the flanking markers provides an important anchor point for the creation of physical continuity across the DGI-II candidate region. 38 refs., 4 figs., 2 tabs.

  10. No Evidence for Association between Amelogenesis Imperfecta and Candidate Genes

    Directory of Open Access Journals (Sweden)

    M Ghandehari Motlagh

    2009-03-01

    Full Text Available "nBackground: Amelogenesis imperfecta (AI is an inherited tooth disorder. Despite the fact that up to now, several gene muta­tions in MMP20, ENAM, AMELX and KLK4 genes have been reported to be associated with AI, many other genes sug­gested to be involved. The main objective of this study was to find the mutations in three major candidate genes including MMP20, ENAM and KLK4 responsible for AI from three Iranian families with generalized hypoplastic phenotype in all teeth. "nMethods: All exon/intron boundaries of subjected genes were amplified by polymerase chain reaction and subjected to direct sequencing."nResults: One polymorphisms was identified in KLK4 exon 2, in one family a homozygous mutation was found in the third base of codon 22 for serine (TCG>TCT, but not in other families. Although these base substitutions have been occurred in the signaling domain, they do not seem to influence the activity of KLK4 protein."nConclusion: Our results might support the further evidence for genetic heterogeneity; at least, in some AI cases are not caused by a gene in these reported candidate genes.

  11. Amelogenesis Imperfecta: 1 Family, 2 Phenotypes, and 2 Mutated Genes.

    Science.gov (United States)

    Prasad, M K; Laouina, S; El Alloussi, M; Dollfus, H; Bloch-Zupan, A

    2016-12-01

    Amelogenesis imperfecta (AI) is a clinically and genetically heterogeneous group of diseases characterized by enamel defects. The authors have identified a large consanguineous Moroccan family segregating different clinical subtypes of hypoplastic and hypomineralized AI in different individuals within the family. Using targeted next-generation sequencing, the authors identified a novel heterozygous nonsense mutation in COL17A1 (c.1873C>T, p.R625*) segregating with hypoplastic AI and a novel homozygous 8-bp deletion in C4orf26 (c.39_46del, p.Cys14Glyfs*18) segregating with hypomineralized-hypoplastic AI in this family. This study highlights the phenotypic and genotypic heterogeneity of AI that can exist even within a single consanguineous family. Furthermore, the identification of novel mutations in COL17A1 and C4orf26 and their correlation with distinct AI phenotypes can contribute to a better understanding of the pathophysiology of AI and the contribution of these genes to amelogenesis.

  12. Minimally invasive rehabilitation of a patient with amelogenesis imperfecta.

    Science.gov (United States)

    Büchi, Dominik; Fehmer, Vincent; Sailer, Irene; Wolleb, Karin; Jung, Ronald

    2014-01-01

    This case report describes a minimally invasive step-by-step approach to treat a patient with amelogenesis imperfecta. This is a genetic developmental disorder of the dental enamel, which clinically manifests as white and dark discolorations of the teeth. The clinical examination did not reveal the true depth of the staining. Therefore, a step-wise treatment approach was chosen. The first step consisted of a home bleaching procedure, which led to a slight improvement of the esthetic appearance, but the stains were still clearly visible. The next step was the application of a microabrasion technique. This led to further improvement, but not to a satisfactory result for this patient who had high esthetic expectations. Thus, the third step was undertaken: it was planned to restore the maxillary incisors and canines with ceramic veneers. The dental technician prepared a wax-up, which served as a basis for a clinical mock-up. After discussing the mock-up and the treatment plan with the patient, crown lengthening was performed on teeth 11 and 23 to improve the pink esthetics. Subsequently, the teeth were prepared in a minimally invasive way and a final impression was taken. Following try-in, the six veneers were inserted with resin cement.

  13. Adenovirus gene transfer to amelogenesis imperfecta ameloblast-like cells.

    Directory of Open Access Journals (Sweden)

    Anton V Borovjagin

    Full Text Available To explore gene therapy strategies for amelogenesis imperfecta (AI, a human ameloblast-like cell population was established from third molars of an AI-affected patient. These cells were characterized by expression of cytokeratin 14, major enamel proteins and alkaline phosphatase staining. Suboptimal transduction of the ameloblast-like cells by an adenovirus type 5 (Ad5 vector was consistent with lower levels of the coxsackie-and-adenovirus receptor (CAR on those cells relative to CAR-positive A549 cells. To overcome CAR -deficiency, we evaluated capsid-modified Ad5 vectors with various genetic capsid modifications including "pK7" and/or "RGD" motif-containing short peptides incorporated in the capsid protein fiber as well as fiber chimera with the Ad serotype 3 (Ad3 fiber "knob" domain. All fiber modifications provided an augmented transduction of AI-ameloblasts, revealed following vector dose normalization in A549 cells with a superior effect (up to 404-fold of pK7/RGD double modification. This robust infectivity enhancement occurred through vector binding to both α(vβ3/α(vβ5 integrins and heparan sulfate proteoglycans (HSPGs highly expressed by AI-ameloblasts as revealed by gene transfer blocking experiments. This work thus not only pioneers establishment of human AI ameloblast-like cell population as a model for in vitro studies but also reveals an optimal infectivity-enhancement strategy for a potential Ad5 vector-mediated gene therapy for AI.

  14. Deletion of ameloblastin exon 6 is associated with amelogenesis imperfecta.

    Science.gov (United States)

    Poulter, James A; Murillo, Gina; Brookes, Steven J; Smith, Claire E L; Parry, David A; Silva, Sandra; Kirkham, Jennifer; Inglehearn, Chris F; Mighell, Alan J

    2014-10-15

    Amelogenesis imperfecta (AI) describes a heterogeneous group of inherited dental enamel defects reflecting failure of normal amelogenesis. Ameloblastin (AMBN) is the second most abundant enamel matrix protein expressed during amelogenesis. The pivotal role of AMBN in amelogenesis has been confirmed experimentally using mouse models. However, no AMBN mutations have been associated with human AI. Using autozygosity mapping and exome sequencing, we identified genomic deletion of AMBN exon 6 in a second cousin consanguineous family with three of the six children having hypoplastic AI. The genomic deletion corresponds to an in-frame deletion of 79 amino acids, shortening the protein from 447 to 368 residues. Exfoliated primary teeth (unmatched to genotype) were available from family members. The most severely affected had thin, aprismatic enamel (similar to that reported in mice homozygous for Ambn lacking exons 5 and 6). Other teeth exhibited thicker but largely aprismatic enamel. One tooth had apparently normal enamel. It has been suggested that AMBN may function in bone development. No clinically obvious bone or other co-segregating health problems were identified in the family investigated. This study confirms for the first time that AMBN mutations cause non-syndromic human AI and that mouse models with disrupted Ambn function are valid.

  15. Target gene analyses of 39 amelogenesis imperfecta kindreds.

    Science.gov (United States)

    Chan, Hui-Chen; Estrella, Ninna M R P; Milkovich, Rachel N; Kim, Jung-Wook; Simmer, James P; Hu, Jan C-C

    2011-12-01

    Previously, mutational analyses identified six disease-causing mutations in 24 amelogenesis imperfecta (AI) kindreds. We have since expanded the number of AI kindreds to 39, and performed mutation analyses covering the coding exons and adjoining intron sequences for the six proven AI candidate genes [amelogenin (AMELX), enamelin (ENAM), family with sequence similarity 83, member H (FAM83H), WD repeat containing domain 72 (WDR72), enamelysin (MMP20), and kallikrein-related peptidase 4 (KLK4)] and for ameloblastin (AMBN) (a suspected candidate gene). All four of the X-linked AI families (100%) had disease-causing mutations in AMELX, suggesting that AMELX is the only gene involved in the aetiology of X-linked AI. Eighteen families showed an autosomal-dominant pattern of inheritance. Disease-causing mutations were identified in 12 (67%): eight in FAM83H, and four in ENAM. No FAM83H coding-region or splice-junction mutations were identified in three probands with autosomal-dominant hypocalcification AI (ADHCAI), suggesting that a second gene may contribute to the aetiology of ADHCAI. Six families showed an autosomal-recessive pattern of inheritance, and disease-causing mutations were identified in three (50%): two in MMP20, and one in WDR72. No disease-causing mutations were found in 11 families with only one affected member. We conclude that mutation analyses of the current candidate genes for AI have about a 50% chance of identifying the disease-causing mutation in a given kindred.

  16. Blood flow controls bone vascular function and osteogenesis

    Science.gov (United States)

    Ramasamy, Saravana K.; Kusumbe, Anjali P.; Schiller, Maria; Zeuschner, Dagmar; Bixel, M. Gabriele; Milia, Carlo; Gamrekelashvili, Jaba; Limbourg, Anne; Medvinsky, Alexander; Santoro, Massimo M.; Limbourg, Florian P.; Adams, Ralf H.

    2016-01-01

    While blood vessels play important roles in bone homeostasis and repair, fundamental aspects of vascular function in the skeletal system remain poorly understood. Here we show that the long bone vasculature generates a peculiar flow pattern, which is important for proper angiogenesis. Intravital imaging reveals that vessel growth in murine long bone involves the extension and anastomotic fusion of endothelial buds. Impaired blood flow leads to defective angiogenesis and osteogenesis, and downregulation of Notch signalling in endothelial cells. In aged mice, skeletal blood flow and endothelial Notch activity are also reduced leading to decreased angiogenesis and osteogenesis, which is reverted by genetic reactivation of Notch. Blood flow and angiogenesis in aged mice are also enhanced on administration of bisphosphonate, a class of drugs frequently used for the treatment of osteoporosis. We propose that blood flow and endothelial Notch signalling are key factors controlling ageing processes in the skeletal system. PMID:27922003

  17. Biomechanics and orthodontic treatment protocol in maxillofacial distraction osteogenesis

    OpenAIRE

    2011-01-01

    As in the traditional combined surgical and orthodontic procedures, an Orthodontist can plays vital role in treatment planning and the orthodontic treatment of patient undergoing distraction osteogenesis. This role includes predistraction assessment of the craniofacial skeleton and occlusal function, pre-distraction, and post-distraction orthodontic care. Based on clinical evaluation, dental study models, photographic analysis, cephalometric evaluation, and three-dimensional computed tomograp...

  18. Modified Dento - Alveolar Distraction Osteogenesis Technique for Rapid Canine Retraction

    Directory of Open Access Journals (Sweden)

    Sameer Patil

    2012-01-01

    Full Text Available Distraction Osteogenesis claims to reduce the duration of treatment as well aid in conservation of anchorage. With the introduction of Dento- alveolar distraction retraction of canine can now be done in about 2-3 weeks with minimal loss of anchorage and little/no root resorption. However, surgical procedure required for dento-alveolar distraction can cause significant swelling and post operative discomfort. Our small modification in the surgical procedure drastically reduces the discomfort and improves patient compliance.

  19. Modified Dento - Alveolar Distraction Osteogenesis Technique for Rapid Canine Retraction

    OpenAIRE

    Sameer Patil; Sharadindu Kotrashetti; Sumit Yadev; Ketan Vhora

    2012-01-01

    Distraction Osteogenesis claims to reduce the duration of treatment as well aid in conservation of anchorage. With the introduction of Dento- alveolar distraction retraction of canine can now be done in about 2-3 weeks with minimal loss of anchorage and little/no root resorption. However, surgical procedure required for dento-alveolar distraction can cause significant swelling and post operative discomfort. Our small modification in the surgical procedure drastically reduces the discomfort an...

  20. A potential role for tetranectin in mineralization during osteogenesis

    DEFF Research Database (Denmark)

    Wewer, U M; Ibaraki, K; Schjørring, P;

    1994-01-01

    cartilage or in the surrounding skeletal muscle. Using an in vitro mineralizing system, we examined osteoblastic cells at different times during their growth and differentiation. Tetranectin mRNA appeared in the cultured osteoblastic cells in parallel with mineralization, in a pattern similar...... osteogenesis. In conclusion, we have established a potential role for tetranectin as a bone matrix protein expressed in time and space coincident with mineralization in vivo and in vitro....

  1. A novel osteogenesis technique: The expansible guided bone regeneration

    OpenAIRE

    Osama Zakaria; Marwa Madi; Shohei Kasugai

    2012-01-01

    Guided bone regeneration is a unique osteogenesis technique that requires a barrier membrane under periosteum to create space for bone regeneration. However, creating sizeable spaces is clinically not commonly feasible. A titanium plate and a thin silicone membrane were surgically layered on each calvaria of eight rabbits. Then, the periphery of the silicone membrane was fixed by a plastic ring to the underlying bone u...

  2. Endothelial Notch activity promotes angiogenesis and osteogenesis in bone

    Science.gov (United States)

    Ramasamy, Saravana K.; Kusumbe, Anjali P.; Wang, Lin; Adams, Ralf H.

    2014-03-01

    Blood vessel growth in the skeletal system and osteogenesis seem to be coupled, suggesting the existence of molecular crosstalk between endothelial and osteoblastic cells. Understanding the nature of the mechanisms linking angiogenesis and bone formation should be of great relevance for improved fracture healing or prevention of bone mass loss. Here we show that vascular growth in bone involves a specialized, tissue-specific form of angiogenesis. Notch signalling promotes endothelial cell proliferation and vessel growth in postnatal long bone, which is the opposite of the well-established function of Notch and its ligand Dll4 in the endothelium of other organs and tumours. Endothelial-cell-specific and inducible genetic disruption of Notch signalling in mice not only impaired bone vessel morphology and growth, but also led to reduced osteogenesis, shortening of long bones, chondrocyte defects, loss of trabeculae and decreased bone mass. On the basis of a series of genetic experiments, we conclude that skeletal defects in these mutants involved defective angiocrine release of Noggin from endothelial cells, which is positively regulated by Notch. Administration of recombinant Noggin, a secreted antagonist of bone morphogenetic proteins, restored bone growth and mineralization, chondrocyte maturation, the formation of trabeculae and osteoprogenitor numbers in endothelial-cell-specific Notch pathway mutants. These findings establish a molecular framework coupling angiogenesis, angiocrine signals and osteogenesis, which may prove significant for the development of future therapeutic applications.

  3. Osteogenesis process of tricalcium phosphate ceramics in vivo

    Institute of Scientific and Technical Information of China (English)

    戴红莲; 李世普; 闫玉华; 李小溪; 贾莉

    2003-01-01

    To investigate the osteogenesis of calcium phosphate ceramics, β-TCP ceramics were implanted into thecondyle femur of rabbits, and tetracycline was injected termly. Specimens were host at 1, 2, 3, 4, 5, 6 months af-ter implanted. The new bone formation and osteogenesis process were observed by the histomorphology, fluorescentmicroscope, SEM and EPMA. The results demonstrate that, osteogenesis is active, there are abundant osteoblastson the surface of osteoid, mesenchymal cell hyperplasia and incursion is found in materials after 1 month. After 2months, there is blood vessel formation and macrophage soakage within materials. Bone-island appears and connectsby bone-bridge after 3 months. β-TCP ceramics degrade and are dispersed by new formation bone. Woven boneturns into bone lamella by rebuilding and calcification. The materials entirely change their original shape and com-bines with bone tissue as a whole after 6 months. The typical structure of spongy bone forms. It is confirmed thatβ-TCP is a degradable biocompatible artificial bone material which can incorporating in life.

  4. Prosthetic and Surgical Approach for Oral Rehabilitation in a Patient with Amelogenesis Imperfecta: A Clinical Report

    Directory of Open Access Journals (Sweden)

    H. Sazegara

    2007-06-01

    Full Text Available Amelogenesis imperfecta is a heterogeneous group of hereditary disorders. Its treatment continues throughout the patients’ childhood and adolescence and consists of advanced restorative care in severe cases.A thorough prosthodontic treatment plan including orthognatic surgery, full veneer crowns and all ceramic anterior crowns is presented in this clinical report.

  5. Hypomaturation amelogenesis imperfecta caused by a novel SLC24A4 mutation.

    Science.gov (United States)

    Herzog, Curtis R; Reid, Bryan M; Seymen, Figen; Koruyucu, Mine; Tuna, Elif Bahar; Simmer, James P; Hu, Jan C-C

    2015-02-01

    In this case report of autosomal recessive pigmented hypomaturation amelogenesis imperfecta (AI), we identify a novel homozygous missense mutation (g.165151 T>G; c.1317 T>G; p.Leu436 Arg) in SLC24A4, a gene encoding a potassium-dependent sodium-calcium exchanger that is critical for hardening dental enamel during tooth development.

  6. Hypomaturation Amelogenesis Imperfecta Caused By A Novel SLC24A4 Mutation

    Science.gov (United States)

    Herzog, Curtis R.; Reid, Bryan M.; Seymen, Figen; Koruyucu, Mine; Tuna, Elif Bahar; Simmer, James P.; Hu, Jan C-C.

    2014-01-01

    In this case report of autosomal recessive pigmented hypomaturation amelogenesis imperfecta (AI), we identify a novel homozygous missense mutation (g.165151T>G; c.1317T>G; p.Leu436Arg) in SLC24A4, a gene encoding a potassium-dependent sodium-calcium exchanger that is critical for hardening dental enamel during tooth development. PMID:25442250

  7. Ceramic Veneers and Direct-Composite Cases of Amelogenesis Imperfecta Rehabilitation.

    Science.gov (United States)

    Shibata, S; Taguchi, Cmc; Gondo, R; Stolf, S C; Baratieri, L N

    2016-01-01

    The aim of this article is to present two case reports for the treatment of patients affected with amelogenesis imperfecta. One case was treated with composite resin and the other case with ceramic veneers. Esthetic and functional results were achieved using both treatments, and a review of advantages and disadvantages is presented.

  8. Distraction osteogenesis after irradiation in a rabbit model

    Energy Technology Data Exchange (ETDEWEB)

    Uehara, Kenji [Kanazawa Univ. (Japan). Graduate School of Medical Science

    2002-06-01

    Little is known about how preoperative irradiation delays distraction osteogenesis. The purpose of this study is to investigate the effect of preoperative irradiation on distraction osteogenesis. A single dose of 15 Gy irradiation was applied in a medial-to-lateral direction to the right rear legs of Japanese white rabbits. This was followed immediately by application of a unilateral external fixator and diaphyseal osteotomy of the tibia. Seven days later, lengthening of the tibia was initiated at a rate of 0.5 mm/day and continued for 4 weeks, with a total elongation of 14 mm. Radiographic and histological findings and microangiography were examined. Radiographs of the legs were obtained once a week. The animals were sacrificed at 0 and 4 weeks after completion of lengthening, and the tibia were subjected to histological examination and microangiography. Routine staining was performed with hematoxyline and eosin, and immunostaining with a vascular endothelial growth factor (VEGF) antibody. The radiographs showed little regeneration during the elongation phase. Although the callus appeared very slowly during the maturation phase, it did not show the usual three distinct zones, but only spotty callus formation. Furthermore, regeneration was not completed until the 4th week of the maturation period. The histological examination at the end of distraction showed a gap in the distraction, consisting of loose connective tissue with part of the fibrous tissue oriented longitudinally. There was no evidence of new mineralization. Four weeks after completion of distraction, the major part of the radiolucent region consisted of cartilage. There was no evidence of the normal regeneration pattern described in many previous reports. The spotty osteogenesis was identified as endochondral ossification. Immunochemical examination of the regeneration area revealed that the blood vessels were extremely localized, and that expression of VEGF in the osteoblasts was very high

  9. Complications of mandibular distraction osteogenesis for developmental deformities: a systematic review of the literature

    NARCIS (Netherlands)

    C.R.A. Verlinden; S.E.C.M. van de Vijfeijken; D.B. Tuinzing; E.P. Jansma; A.G. Becking; G.R.J. Swennen

    2015-01-01

    A systematic review of English and non-English articles on the complications of mandibular distraction osteogenesis (MDO) for patients with developmental deformities was performed, in accordance with the PRISMA statement. Search terms expressing distraction osteogenesis were used in ‘AND’ combinatio

  10. Complications of mandibular distraction osteogenesis for acquired deformities: a systematic review of the literature

    NARCIS (Netherlands)

    C.R.A. Verlinden; S.E.C.M. van de Vijfeijken; D.B. Tuinzing; A.G. Becking; G.R.J. Swennen

    2015-01-01

    A systematic review on complications in all forms of mandibular distraction osteogenesis (MDO) for acquired deformities was performed. Search terms expressing distraction osteogenesis were used in ‘AND’ combination with search terms comprising ‘mandible’ and terms for complication, failure, and morb

  11. Determinantes da marcha independente na osteogênese imperfeita Independent walk in osteogenesis imperfect

    Directory of Open Access Journals (Sweden)

    Carmem Lia Martins Moreira

    2011-01-01

    Full Text Available OBJETIVOS: Investigar o processo de locomoção em pacientes com osteogênese imperfeita (OI e os fatores que o influenciam, sublinhando pontos clínicos relevantes à reabilitação motora. MÉTODOS: Estudo transversal, retrospectivo, realizado no ambulatório de fisioterapia motora do Instituto Fernandes Figueira. Foram incluídos todos os pacientes com diagnóstico clínico de OI. Foram excluídos os que apresentavam comorbidades e idade inferior a dois anos. Utilizou-se o Epi-Info versão 3.4 para construção do banco de dados e o SPSS versão 15 para análise estatística. Foi calculado risco relativo para mensurar associação de características clínicas com a marcha independente, adotando-se nível de significância de 5% para as análises. RESULTADOS: Foram incluídos 69 pacientes. Dentre eles, 43,5% tinham OI tipo I; 37,7% tipo III e 18,8% tipo IV. 76,8% apresentavam deformidades em ossos longos. Observou-se associação negativa entre hipotonia, número de fraturas e marcha independente e positiva entre marcha independente e OI tipo I. CONCLUSÕES: A clínica fisioterápica, como complementar à ortopédica e à administração de fármacos da família dos bifosfonatos, é de fundamental importância para a reabilitação da capacidade motora dos indivíduos com OI. Nivel de Evidência, estudos transversais.OBJECTIVES: Investigation of the locomotion process in patients with osteogenesis imperfecta (OI, and the factors that influence it, with special attention to clinical aspects relating to motor rehabilitation. METHODS: a retrospective, cross-sectional study was carried out at the physical therapy outpatient clinic of the Instituto Fernandes Figueira. All patients with a clinical diagnosis of OI were included. Patients with other diseases, and those aged under two years, old were excluded. Epi-Info version 3.4 was used to construct the database, and SPSS version 15 for the statistical analysis. RESULTS: The odds-ratio was used to

  12. Mutation Analysis of COL1A1 and COL1A2 in Fetuses with Osteogenesis Imperfecta Type II/III.

    Science.gov (United States)

    Wang, Wenbo; Wu, Qichang; Cao, Lin; Sun, Li; Xu, Yasong; Guo, Qiwei

    2015-01-27

    Aim: To analyze COL1A1/2 mutations in prenatal-onset OI for determine the proportion of mutations in type I collagen genes among prenatal onset OI and to provide additional data for genotype-phenotype analyses. Material and Methods: Ten cases of severe fetal short-limb dwarfism detected by antenatal ultrasonography were referred to our center. Before the termination of pregnancy, cordocentesis was performed for fetal karyotype and COL1A1/2 gene sequencing analysis. Postmortem radiographic examination was performed at all instances for definitive diagnosis. Results: COL1A1 and COL1A2 SNP and mutations were identified in all the cases. Among these, one synonymous SNP and four synonymous SNPs were recognized in COL1A1/2, respectively, seven cases have distinct heterozygous mutations and six new COL1A1/2 gene mutations were identified. Conclusion: There has been substantial progress in the identification of the molecular defects responsible for skeletal dysplasias. With the constant increase in the number of identified mutations in COL1A1 and COL1A2, genotype-phenotype correlation is becoming increasingly pertinent. © 2015 S. Karger AG, Basel.

  13. 成骨不全分子遗传学研究进展%Advance of Genetic Studies on Osteogenesis Imperfecta

    Institute of Scientific and Technical Information of China (English)

    吴晓林; 顾鸣敏; 王铸钢

    2006-01-01

    成骨不全病(OMIM 166200)是一种常染色体显性遗传病,其临床表现以骨折及结缔组织异常为特征.90%以上病例的发生与形成Ⅰ型胶原的两个基因(COL1A1和COL1A2)突变有关.该病也存在遗传异质性.成骨不全的表型变异范围较广,临床分型复杂,且不同表型的分子机制也不同.现对该病的临床分型及分子遗传学研究进展作一综述.

  14. 家族性成骨不全症2例报告%Report of two cases of familial osteogenesis imperfecta

    Institute of Scientific and Technical Information of China (English)

    程庆丰; 张素华; 李启富; 郑瑞芝; 青华; 刘隆田

    2008-01-01

    目的 总结帕米膦酸钠在成骨不全症中的应用经验.方法 对2007年我院收治的2例成骨不全症的治疗进行回顾分析.结果 两例对帕米膦酸钠有较好耐受性.治疗随访期间未再发骨折.结论 帕米膦酸钠对成骨不全症有较好疗效,但需更多病例观察.

  15. 双膦酸盐治疗成骨不全研究进展%Bisphosphonate in treatment of osteogenesis imperfecta: an update

    Institute of Scientific and Technical Information of China (English)

    石长贵; 张颖; 袁文

    2014-01-01

    成骨不全是一组以骨骼脆性增加及胶原代谢紊乱为特征的全身性结缔组织疾病,主要由编码Ⅰ型胶原的基因发生突变所致,此病以骨脆性增加、骨关节进行性畸形、蓝巩膜、牙本质发育不全及听力下降为常见表现.目前治疗成骨不全的最理想的药物是双膦酸盐,本文复习国内外相关文献,就其治疗的最适剂量与时间、最佳给药途径、最佳药物选择以及药物与成骨不全类型和患者年龄的最适匹配等问题的研究进展作一综述.

  16. Radiological Features and Diagnosis of Osteogenesis Imperfecta%成骨不全的影像学表现与诊断

    Institute of Scientific and Technical Information of China (English)

    徐忠建; 丁海霞; 鲁植艳; 詹友军

    2010-01-01

    收集16例成骨不全患者及2例胎儿成骨不全患者的X线平片及临床资料,观察及分析X线表现特点.成骨不全患者主要有多发性骨折、骨膜反应、干骺端硬化,骨形态改变、四肢关节改变以及脊柱侧凸颅底凹陷征、骨量减少等.熟悉这些特征可作出诊断.

  17. 骨肽治疗成骨不全症临床观察%Clinical effect of ossotide infection on osteogenesis imperfecta

    Institute of Scientific and Technical Information of China (English)

    陈福全

    2005-01-01

    目的观察骨肽治疗成骨不全症的临床疗效.方法选择成骨不全症患者40例分成两组,骨肽为治疗组20例,其他方法20例,治疗1、2疗程后,将两组进性对比分析.结果两组比较治疗组总有效率达95%以上,对照组总有效率60%,两组差异有显著性(P<0.01).结论骨肽治疗成骨不全症是一种有效的药物,治疗方法简便,效果好,安全,适合各层次的医疗单位.

  18. 脆骨症伴双侧跟骨鸟嘴型骨折1例%Bilateral bird mouth type fracture of calcaneus with osteogenesis imperfecta

    Institute of Scientific and Technical Information of China (English)

    周礼智; 马本山

    2001-01-01

    @@ 1病例资料 患者,女,15岁,左跟部跌伤1 h入院.既往有多次骨折史,其母为脆骨症患者.检查:身体矮小,蓝巩膜,周身关节松驰.左前臂掌侧成角畸形,右肘内翻.左跟部皮肤青紫、畸形,摸到向后上移位突出的骨块.

  19. Osteogenesis imperfecta with metaphyseal dysplasia: report of one case%成骨不全合并干骺端发育异常1例

    Institute of Scientific and Technical Information of China (English)

    李玉清; 何海潮; 丁建平; 王溱

    2005-01-01

    @@ 病例男,2.5岁.因多次骨折入院.查体:身材矮小,股骨远端膨大畸形,压痛,有蓝色巩膜.X线表现:诸骨骨质密度低,胫腓骨、肱骨、尺桡骨纤细,皮质菲薄.双侧尺桡骨弯曲,左桡骨见骨折线(图1).左胫骨及右桡骨可见局限性骨膜新生骨形成(图2),双股骨远端粗大、膨胀,皮质菲薄,左侧皮质断裂,双股骨皮质毛糙(图3).腕骨出现2个.肋骨纤细.椎体密度低,变扁,有的呈双凹变形,椎间隙增宽(图4).骨骺未见异常.X线诊断:成骨不全合并干骺端发育异常.

  20. Nursing care of 1 child with osteogenesis imperfecta congenita%1例先天性成骨不全症患儿的护理

    Institute of Scientific and Technical Information of China (English)

    翁湘

    2011-01-01

    @@ 先天性成骨不全症又名脆骨症,为全身性结缔组织病,是临床上少见的疾病.该病遭受轻微外力便容易发生病理性骨折,对护理有很高的要求.本科于2010年3月17日收治1例先天性成骨不全患儿,现将临床特点与护理介绍如下.

  1. Stability after Cleft Maxillary Distraction Osteogenesis or Conventional Orthognathic Surgery

    Directory of Open Access Journals (Sweden)

    Kristian Andersen

    2015-06-01

    Full Text Available Objectives: To compare stability of maxillary advancements in patients with cleft lip and palate following distraction osteogenesis or orthognathic surgery. Material and Methods: Inclusion criteria: 1 cleft lip and palate, 2 advancement > 8 mm. Eleven patients comprised the distraction osteogenesis group (DOG. Seven patients comprised the orthognathic treatment group (CONVG. Skeletal and soft tissue points were traced on lateral cephalograms: T1 (preoperatively, T2 (after surgery, T3 (follow-up. Group differences were analyzed using Students t-test. Results: At T1-T2, advancement of 6.98 mm (P = 0.002 was observed in DOG. Horizontal overjet increased 11.62 mm (P = 0.001. A point-nasion-B point (ANB angle increased 8.82° (P = 0.001. Aesthetic plane to upper lip was reduced 5.44 mm (P = 0.017 and the naso-labial angle increased 16.6° (P = 0.001. Vertical overbite (VOB increased 2.27 mm (P = 0.021. In T2-T3, no significant changes were observed in DOG. In T1-T2, horizontal overjet increased 8.45 mm (P = 0.02. The ANB angle, 9.33° (P = 0.009 in CONVG. At T2-T3, VOB increased, 2.35 mm (P = 0.046, and the ANB angle reduced, 3.83° (P = 0.003. In T2-T3, no parameters changed in CONVG. At follow-up (T3, VOB increased in CONVG compared with DOG, (P = 0.01. Vertical position of A point differed between the groups (P = 0.04. No significant intergroup differences between soft tissue parameters occurred. Conclusions: Distraction osteogenesis resulted in a stable position of the maxilla and movement upwards in vertical plane, however in case of orthognathic treatment sagittal relapse and a continued postoperatively downward movement was registered.

  2. Stability after Cleft Maxillary Distraction Osteogenesis or Conventional Orthognathic Surgery

    DEFF Research Database (Denmark)

    Andersen, Kristian; Svenstrup, Martin; Pedersen, Thomas Klit

    2015-01-01

    OBJECTIVES: To compare stability of maxillary advancements in patients with cleft lip and palate following distraction osteogenesis or orthognathic surgery. MATERIAL AND METHODS: INCLUSION CRITERIA: 1) cleft lip and palate, 2) advancement > 8 mm. Eleven patients comprised the distraction.......98 mm (P = 0.002) was observed in DOG. Horizontal overjet increased 11.62 mm (P = 0.001). A point-nasion-B point (ANB) angle increased 8.82° (P = 0.001). Aesthetic plane to upper lip was reduced 5.44 mm (P = 0.017) and the naso-labial angle increased 16.6° (P = 0.001). Vertical overbite (VOB) increased...

  3. A novel mutation in the DSPP gene associated with dentinogenesis imperfecta type II.

    Science.gov (United States)

    Lee, S-K; Lee, K-E; Jeon, D; Lee, G; Lee, H; Shin, C-U; Jung, Y-J; Lee, S-H; Hahn, S-H; Kim, J-W

    2009-01-01

    Hereditary dentin defects are divided into dentinogenesis imperfecta and dentin dysplasia. We identified a family segregating severe dentinogenesis imperfecta. The kindred spanned four generations and showed an autosomal-dominant pattern of inheritance. The proband was a child presenting with a severely affected primary dentition, with wide-open pulp chambers and multiple pulp exposures, resembling a DGI type III (DGI-III) pattern. We hypothesized that a mutation in the DSPP gene is responsible for this severe phenotype. Mutational analyses revealed a novel mutation (c.53T>A, p.V18D) near the intron-exon boundary in the third exon of the DSPP gene. We analyzed the effect of the mutation by means of an in vitro splicing assay, which revealed that the mutation did not affect pre-mRNA splicing. Further studies are needed for a better understanding of the nature of the disease and the development of an appropriate treatment strategy.

  4. Dental management of amelogenesis imperfecta patients: a primer on genotype-phenotype correlations.

    Science.gov (United States)

    Ng, F K; Messer, L B

    2009-01-01

    Amelogenesis imperfecta (AI) represents a group of hereditary conditions which affects enamel formation in the primary and permanent dentitions. Mutations in genes critical for amelogenesis result in diverse phenotypes characterized by variably thin and/or defective enamel. To date, mutations in 5 genes are known to cause AI in humans. Understanding the molecular etiologies and associated inheritance patterns can assist in the early diagnosis of this condition. Recognition of genotype-phenotype correlations will allow clinicians to guide genetic testing and select appropriate management strategies for patients who express different phenotypes. The purpose of this paper was to provide a narrative review of the current literature on amelogenesis imperfecta, particularly regarding recent advances in the identification of candidate genes and the patterns of inheritance.

  5. Defining a new candidate gene for amelogenesis imperfecta: from molecular genetics to biochemistry.

    Science.gov (United States)

    Urzúa, Blanca; Ortega-Pinto, Ana; Morales-Bozo, Irene; Rojas-Alcayaga, Gonzalo; Cifuentes, Víctor

    2011-02-01

    Amelogenesis imperfecta is a group of genetic conditions that affect the structure and clinical appearance of tooth enamel. The types (hypoplastic, hypocalcified, and hypomature) are correlated with defects in different stages of the process of enamel synthesis. Autosomal dominant, recessive, and X-linked types have been previously described. These disorders are considered clinically and genetically heterogeneous in etiology, involving a variety of genes, such as AMELX, ENAM, DLX3, FAM83H, MMP-20, KLK4, and WDR72. The mutations identified within these causal genes explain less than half of all cases of amelogenesis imperfecta. Most of the candidate and causal genes currently identified encode proteins involved in enamel synthesis. We think it is necessary to refocus the search for candidate genes using biochemical processes. This review provides theoretical evidence that the human SLC4A4 gene (sodium bicarbonate cotransporter) may be a new candidate gene.

  6. Dental Management of a Child with Dentinogenesis Imperfecta: A Case Report

    Directory of Open Access Journals (Sweden)

    Najmeh Akhlaghi

    2016-10-01

    Full Text Available Dentinogenesis imperfecta (DI is a hereditary dentin defect caused by an autosomal dominant mutation in dentin sialophosphoprotein gene. Defective dentin development results in discolored teeth that are prone to wear and fracture. Early diagnosis and proper treatment are necessary to achieve better functional and esthetic results and minimize nutritional deficiencies and psychosocial distress. In order to prevent excessive loss of tooth structure, placement of stainless steel crowns (SSCs on deciduous and young permanent posterior teeth is recommended as soon as such teeth erupt. This clinical report presents the clinical manifestations and management of a 3.5-year-old child diagnosed with DI type II.Keywords: Dentin; Dentinogenesis Imperfecta; Tooth, Deciduous

  7. Limited phenotypic variation of hypocalcified amelogenesis imperfecta in a danish five-generation family with a novel FAM83H nonsense mutation

    DEFF Research Database (Denmark)

    Haubek, Dorte; Gjørup, Hans; Jensen, Lillian Gryesten

    2011-01-01

    Limited phenotypic variation of hypocalcified amelogenesis imperfecta in a danish five-generation family with a novel FAM83H nonsense mutation......Limited phenotypic variation of hypocalcified amelogenesis imperfecta in a danish five-generation family with a novel FAM83H nonsense mutation...

  8. Miniature osmotic actuators for controlled maxillofacial distraction osteogenesis

    Science.gov (United States)

    Li, Yu-Hsien; Su, Yu-Chuan

    2010-06-01

    We have successfully demonstrated miniature actuators that are capable of converting chemical potential directly into steady mechanical movements for maxillofacial distraction osteogenesis. Pistons and diaphragms powered by osmosis are employed to provide the desired linear and volumetric displacements for bone distraction and potentially the release of bone morphogenetic proteins, respectively. The cylindrical-shaped miniature actuators are composed of polymeric materials and fabricated by molding and assembly processes. In the prototype demonstration, vapor-permeable thermoplastic polyurethane was employed as the semi-permeable material. 3 cm long actuators with piston and diaphragm radii of 1 mm and 500 µm, respectively, were fabricated and characterized. The maximum distraction force from the piston-type actuator is found to be 6 N while the piston travels at a constant velocity of 32 µm h-1 (or 0.77 mm/day) for about 1 week. Meanwhile, the release rate from the diaphragm-type actuator is measured to be constant, 0.15 µl h-1 (or 3.6 µl/day), throughout the experiment. Moreover, the sizes and output characteristics of the self-regulating actuators could readily be tailored to realize optimal distraction rate, rhythm and osteogenic activity. As such, the demonstrated miniature osmotic actuators could potentially serve as versatile apparatuses for maxillofacial distraction osteogenesis and fulfill the needs of a variety of implantable and biomedical applications.

  9. Glycosylation of Dentin Matrix Protein 1 is critical for osteogenesis.

    Science.gov (United States)

    Sun, Yao; Weng, Yuteng; Zhang, Chenyang; Liu, Yi; Kang, Chen; Liu, Zhongshuang; Jing, Bo; Zhang, Qi; Wang, Zuolin

    2015-12-04

    Proteoglycans play important roles in regulating osteogenesis. Dentin matrix protein 1 (DMP1) is a highly expressed bone extracellular matrix protein that regulates both bone development and phosphate metabolism. After glycosylation, an N-terminal fragment of DMP1 protein was identified as a new proteoglycan (DMP1-PG) in bone matrix. In vitro investigations showed that Ser(89) is the key glycosylation site in mouse DMP1. However, the specific role of DMP1 glycosylation is still not understood. In this study, a mutant DMP1 mouse model was developed in which the glycosylation site S(89) was substituted with G(89) (S89G-DMP1). The glycosylation level of DMP1 was down-regulated in the bone matrix of S89G-DMP1 mice. Compared with wild type mice, the long bones of S89G-DMP1 mice showed developmental changes, including the speed of bone remodeling and mineralization, the morphology and activities of osteocytes, and activities of both osteoblasts and osteoclasts. These findings indicate that glycosylation of DMP1 is a key posttranslational modification process during development and that DMP1-PG functions as an indispensable proteoglycan in osteogenesis.

  10. Osteogenic Matrix Cell Sheets Facilitate Osteogenesis in Irradiated Rat Bone

    Directory of Open Access Journals (Sweden)

    Yoshinobu Uchihara

    2015-01-01

    Full Text Available Reconstruction of large bone defects after resection of malignant musculoskeletal tumors is a significant challenge in orthopedic surgery. Extracorporeal autogenous irradiated bone grafting is a treatment option for bone reconstruction. However, nonunion often occurs because the osteogenic capacity is lost by irradiation. In the present study, we established an autogenous irradiated bone graft model in the rat femur to assess whether osteogenic matrix cell sheets improve osteogenesis of the irradiated bone. Osteogenic matrix cell sheets were prepared from bone marrow-derived stromal cells and co-transplanted with irradiated bone. X-ray images at 4 weeks after transplantation showed bridging callus formation around the irradiated bone. Micro-computed tomography images at 12 weeks postoperatively showed abundant callus formation in the whole circumference of the irradiated bone. Histology showed bone union between the irradiated bone and host femur. Mechanical testing showed that the failure force at the irradiated bone site was significantly higher than in the control group. Our study indicates that osteogenic matrix cell sheet transplantation might be a powerful method to facilitate osteogenesis in irradiated bones, which may become a treatment option for reconstruction of bone defects after resection of malignant musculoskeletal tumors.

  11. Scanning electron microscopy and calcification in amelogenesis imperfecta in anterior and posterior human teeth

    OpenAIRE

    Sánchez-Quevedo, M. C.; Ceballos, G.; García, J. M.; Rodriguez, I. A.; Gómez de Ferraris, M. E.; Campos, Antonio

    2001-01-01

    Teeth fragments from members of a famil? clinically and genetically diagnosed as having amelogenesis imperfecta were studied by scanning electron microscopy and X-ray microprobe analysis to establish the morphological patterns and the quantitative concentration of calcium in the enamel of anterior (canine, incisor) and posterior (premolar and molar) teeth. The prism patterns in the enamel of teeth from both regions were parallel or irregularly decussate, with ...

  12. Dentinogenesis imperfecta: A review and case report of a family over four generations

    Directory of Open Access Journals (Sweden)

    Bhandari Sudhir

    2008-01-01

    Full Text Available Dentinogenesis imperfecta (DGI is one of the most common hereditary disorders of dentin formation. It follows an autosomal dominant pattern of transmission, affecting both the formation and mineralization of dentin. Either or both primary and permanent dentition is affected by it. This paper briefly reviews the manifestations of DGI Type II (DGI1 and presents a case report of a family affected with DGI1 over four generations.

  13. Dentinogenesis imperfecta: a case report of comprehensive treatment for a teenager.

    Science.gov (United States)

    Biethman, Rick; Capati, Laura Richards; Eldger, Nicole

    2014-01-01

    Improving a smile can change a person's self-image. This case report describes treatment for an adolescent boy with dentinogenesis imperfecta. Soon to begin high school, the 14-year-old patient was severely obese and disliked his stained teeth. A combination of surgical periodontal treatment, endodontic treatment, and veneers improved both his smile and self-perception-which may have played a role in achieving his weight loss goal of 125 lb at 12 months post-treatment.

  14. Diagnostic features and pedodontic-orthodontic management in dentinogenesis imperfecta type II: a case report.

    Science.gov (United States)

    Huth, K Ch; Paschos, E; Sagner, T; Hickel, R

    2002-09-01

    Dentinogenesis imperfecta type II, also known as hereditary opalescent dentin, is an isolated inherited condition transmitted as an autosomal dominant trait affecting the primary and permanent dentition. The combined pedodontic-orthodontic management of a 4-year-old child is described. Following orthodontic analysis to encourage a favourable growth outcome, treatment comprised restoration of the primary teeth with stainless steel crowns and composite crowns. Differential diagnosis and alternative therapies, including orthodontic considerations, are discussed.

  15. Dentinogenesis imperfecta: a review and case report of a family over four generations.

    Science.gov (United States)

    Bhandari, Sudhir; Pannu, Karneev

    2008-01-01

    Dentinogenesis imperfecta (DGI) is one of the most common hereditary disorders of dentin formation. It follows an autosomal dominant pattern of transmission, affecting both the formation and mineralization of dentin. Either or both primary and permanent dentition is affected by it. This paper briefly reviews the manifestations of DGI Type II (DGI1) and presents a case report of a family affected with DGI1 over four generations.

  16. Aesthetic And Functional Rehabilitation Of The Primary Dentition Affected By Amelogenesis Imperfecta.

    OpenAIRE

    Maria Carolina Salomé Marquezin; Bruna Raquel Zancopé; Larissa Ferreira Pacheco; Maria Beatriz Duarte Gavião; Fernanda Miori Pascon

    2015-01-01

    The objective of this case report was to describe the oral rehabilitation of a five-year-old boy patient diagnosed with amelogenesis imperfecta (AI) in the primary dentition. AI is a group of hereditary disorders that affects the enamel structure. The patient was brought to the dental clinic complaining of tooth hypersensitivity during meals. The medical history and clinical examination were used to arrive at the diagnosis of AI. The treatment was oral rehabilitation of the primary molars wit...

  17. Missense Mutation in Fam83H Gene in Iranian Patients with Amelogenesis Imperfecta.

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    S Jalal Pourhashemi

    2014-12-01

    Full Text Available Amelogenesis Imperfecta (AI is a disorder of tooth development where there is an abnormal formation of enamel or the external layer of teeth. The aim of this study was to screen mutations in the four most important candidate genes, ENAM, KLK4, MMP20 and FAM83H responsible for amelogenesis imperfect.Geneomic DNA was isolated from five Iranian families with 22 members affected with enamel malformations. The PCR amplifications were typically carried out for amplification the coding regions for AI patients and unaffected family members. The PCR products were subjected to direct sequencing. The pedigree analysis was performed using Cyrillic software.One family had four affected members with autosomal dominant hypocalcified amelogenesis imperfecta (ADHPCAI; pedigree analysis revealed four consanguineous families with 18 patients with autosomal recessive hypoplastic amelogenesis imperfecta (ARHPAI. One non-synonymous single-nucleotide substitution, c.1150T>A, p. Ser 342Thr was identified in the FAM83H, which resulted in ADHCAI. Furthermore, different polymorphisms or unclassified variants were detected in MMP20, ENAM and KLK4.Our results are consistent with other studies and provide further evidence for pathogenic mutations of FAM83H gene. These findings suggest different loci and genes could be implicated in the pathogenesis of AI.

  18. Osteogenesis and mineralization in a rabbit mandibular distraction osteogenesis model is promoted by the human LMP-1 gene.

    Science.gov (United States)

    Jiang, Xiaowen; Chen, Yanzhe; Fan, Xiaosheng; Zhang, Hao; Kun, Lu

    2015-04-01

    To observe the effects of LIM mineralization protein-1 (LMP-1) on bone regeneration in the distraction zone based on gene transduction, 36 New Zealand white rabbits underwent mandibular lengthening with a distraction rate of 2 mm/day. The animals were then randomly divided into group A and group B (n = 18, each). At the end of the distraction, Ad5-EGFP viruses and Ad5-LMP-1/EGFP viruses were injected into the distraction gaps in groups A and B, respectively. Seven days later, five randomly selected animals from each group were sacrificed to evaluate the survival of the virus. Four and 8 weeks after distraction osteogenesis (DO), six samples randomly selected from each group underwent CT scanning and dual energy X-ray absorptiometry detection. Eight weeks after DO, the rabbits were sacrificed, and the distracted mandibles were harvested. Six animals from each group processed for radiography, micro-CT, histology, and the rest samples were taken three-point bend testing. Using this model, better bone formation and mineralization in the distracted callus were observed in group B when compared with those in group A. The results suggest local transduction with LMP-1 gene promotes osteogenesis and mineralization in DO.

  19. Alveolar distraction osteogenesis applications in cleft lip and palate patients: a literature review

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    Öznur Mülayim

    2016-05-01

    Full Text Available Distraction osteogenesis technique has been successfully applied in the craniofacial area for long time, and it is being applied increasingly more in cleft lip and palate patients also. Especially in large cleft palate cases, bone grafting or surgical procedures such as distraction osteogenesis can be applied in order to ensure a smooth alveolar arc. In this literature review, alveolar (segmental distraction osteogenesis applications in patients with cleft lip and palate, indications of the technique, advantages and disadvantages, application methods and types of appliances used for this purpose have been evaluated. As conclusion, especially with the application of alveolar (segmental distraction osteogenesis, successful outcome can be achieved in cleft lip and palate patients with velopharyngeal insufficiency, maxillary hypoplasia and maxillary crowding, and this technique may be an alternative to conventional osteotomies and extraoral distractions.

  20. EXPRESSION OF ACTIVIN DURING THE MANDIBULAR DISTRACTION OSTEOGENESIS IN RABBIT

    Institute of Scientific and Technical Information of China (English)

    李昕; 祁佐良; 王炜; 董佳生; 林晓曦; 戴传昌

    2002-01-01

    Objective To investigate the role of activin on osteogenesis during mandibular distraction.Methods Rabbit mandibular distraction model was used and the new regenerating tissue in the distraction zone were harvested at different time points. lmmunohistochemical technique for activin A was performed in the harvested tissues. Results Positive stain was noted in early phases of distraction. At the end of distraction phase osteoblasts and osteoid in primary mineralization front were strongly stained and osteoblasts and osteocytes in peripheral new bone zone were moderately stained. There were also broad activin A stains in osteoblasts and active osteocytes in early consolidation phase. Conclusion The expression of activin is increased during mandibular distraction. It could play an important role in the process of osteoblastic cells secretion, differentiation to osteocytes and bone formation during mandibular distraction.