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    557 results match your criteria Fibrodysplasia Ossificans

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    The Rare Bone Disease Working Group: report from the 2016 American Society for Bone and Mineral Research Annual Meeting.
    Bone 2017 Jan 20. Epub 2017 Jan 20.
    Division of Endocrinology and Metabolism and the Institute for Human Genetics, Department of Medicine, University of California, San Francisco, CA, United States.
    A working group on rare bone diseases was held in Atlanta, Georgia as part of the 2016 annual meeting of the American Society for Bone and Mineral Research. The meeting was organized by Matthew Drake. Given recent advances in our understanding of fibrodysplasia ossificans progressiva (FOP), the initial portion of the program was devoted to basic, translational, and clinical aspects of FOP. Read More

    Integrating Gene Correction in the Reprogramming and Transdifferentiation Processes: A One-Step Strategy to Overcome Stem Cell-Based Gene Therapy Limitations.
    Stem Cells Int 2016 15;2016:2725670. Epub 2016 Dec 15.
    Medical Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon 34054, Republic of Korea.
    The recent advent of induced pluripotent stem cells (iPSCs) and gene therapy tools has raised the possibility of autologous cell therapy for rare genetic diseases. However, cellular reprogramming is inefficient in certain diseases such as ataxia telangiectasia, Fanconi anemia, LIG4 syndrome, and fibrodysplasia ossificans progressiva syndrome, owing to interference of the disease-related genes. To overcome these therapeutic limitations, it is necessary to fundamentally correct the abnormal gene during or prior to the reprogramming process. Read More

    Analog Method for Radiographic Assessment of Heterotopic Bone in Fibrodysplasia Ossificans Progressiva.
    Acad Radiol 2017 Mar 15;24(3):321-327. Epub 2016 Dec 15.
    Division of Geriatric Medicine & Gerontology, Mayo Clinic College of Medicine, Rochester, Minnesota.
    Rationale And Objectives: Severe progressive multifocal heterotopic ossification (HO) is a rare occurrence seen predominantly in patients who have fibrodysplasia ossificans progressiva (FOP) and is difficult to quantitate owing to patient-, disease-, logistical-, and radiation-related issues. The purpose of this study was to develop and validate a scoring system based on plain radiographs for quantitative assessment of HO lesions in patients with FOP.

    Materials And Methods: Institutional review board approval was obtained from the University of Pennsylvania, and all data comply with Health Insurance Portability and Accountability Act regulations. Read More

    mTOR inhibition and BMP signaling act synergistically to reduce muscle fibrosis and improve myofiber regeneration.
    JCI Insight 2016 Dec 8;1(20):e89805. Epub 2016 Dec 8.
    Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan, USA.
    Muscle trauma is highly morbid due to intramuscular scarring, or fibrosis, and muscle atrophy. Studies have shown that bone morphogenetic proteins (BMPs) reduce muscle atrophy. However, increased BMP signaling at muscle injury sites causes heterotopic ossification, as seen in patients with fibrodysplasia ossificans progressiva (FOP), or patients with surgically placed BMP implants for bone healing. Read More

    Early Recognition of Fibrodysplasia Ossificans Progressiva-Important For the Clinician.
    JNMA J Nepal Med Assoc 2016 Apr-Jun;54(202):91-93
    Maulana Azad Medical College, New Delhi, India.
    Fibrodysplasia ossificans progressiva is a rare disorder of heterotopic ossification. Procedures like biopsy and surgery are known to be aggravating factors in promoting heterotopic ossification Clues to clinical diagnosis may therefore be a great advantage to treating orthopedician. Valgus deformity of great toe is an important diagnostic clue for treating physicians and thus aids in preventing the clinicians from subjecting the patients to unnecessary invasive and traumatic procedures. Read More

    Trace element and cytokine concentrations in patients with Fibrodysplasia Ossificans Progressiva (FOP): A case control study.
    J Trace Elem Med Biol 2017 Jan 4;39:186-192. Epub 2016 Oct 4.
    Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité - Universitätsmedizin Berlin, Germany. Electronic address:
    Fibrodysplasia Ossificans Progressiva (FOP) is a rare inherited disease characterized by progressive heterotopic ossification. Disease onset, severity and symptoms vary between FOP patients, as does the frequency and activity of so-called flare-ups, during which tendons, ligaments, muscle and soft tissue are replaced by bone. Traumata, infections or other stressors are known inducers of flare-ups, and the hormone Activin A may be involved in disease activity; however, reliable biomarkers for FOP activity are missing, and the basal trace element and inflammatory state of patients are unknown. Read More

    Two tissue-resident progenitor lineages drive distinct phenotypes of heterotopic ossification.
    Sci Transl Med 2016 Nov;8(366):366ra163
    Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
    Fibrodysplasia ossificans progressiva (FOP), a congenital heterotopic ossification (HO) syndrome caused by gain-of-function mutations of bone morphogenetic protein (BMP) type I receptor ACVR1, manifests with progressive ossification of skeletal muscles, tendons, ligaments, and joints. In this disease, HO can occur in discrete flares, often triggered by injury or inflammation, or may progress incrementally without identified triggers. Mice harboring an Acvr1(R206H) knock-in allele recapitulate the phenotypic spectrum of FOP, including injury-responsive intramuscular HO and spontaneous articular, tendon, and ligament ossification. Read More

    Scleraxis-Lineage Cells Contribute to Ectopic Bone Formation in Muscle and Tendon.
    Stem Cells 2016 Nov 8. Epub 2016 Nov 8.
    Department of Surgery, Section of Plastic Surgery, Burn/Wound and Regenerative Medicine Laboratory, University of Michigan, Michigan, USA.
    The pathologic development of heterotopic ossification (HO) is well described in patients with extensive trauma or with hyperactivating mutations of the bone morphogenetic protein (BMP) receptor ACVR1. However, identification of progenitor cells contributing to this process remains elusive. Here we show that connective tissue cells contribute to a substantial amount of HO anlagen caused by trauma using postnatal, tamoxifen-inducible, scleraxis-lineage restricted reporter mice (Scx-creERT2/tdTomato(fl/fl) ). Read More

    The Fibrodysplasia Ossificans Progressiva (FOP) mutation p.R206H in ACVR1 confers an altered ligand response.
    Cell Signal 2017 Jan 4;29:23-30. Epub 2016 Oct 4.
    Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité Virchow Campus, Berlin, Germany; Charité - Universitätsmedizin Berlin, Berlin, Germany; Berlin Brandenburg School for Regenerative Therapies (BSRT), Berlin, Germany. Electronic address:
    Patients with Fibrodysplasia Ossificans Progressiva (FOP) suffer from ectopic bone formation, which progresses during life and results in dramatic movement restrictions. Cause of the disease are point mutations in the Activin A receptor type 1 (ACVR1), with p.R206H being most common. Read More

    BMP-SMAD-ID promotes reprogramming to pluripotency by inhibiting p16/INK4A-dependent senescence.
    Proc Natl Acad Sci U S A 2016 Nov 28;113(46):13057-13062. Epub 2016 Oct 28.
    Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158;
    Fibrodysplasia ossificans progressiva (FOP) patients carry a missense mutation in ACVR1 [617G > A (R206H)] that leads to hyperactivation of BMP-SMAD signaling. Contrary to a previous study, here we show that FOP fibroblasts showed an increased efficiency of induced pluripotent stem cell (iPSC) generation. This positive effect was attenuated by inhibitors of BMP-SMAD signaling (Dorsomorphin or LDN1931890) or transducing inhibitory SMADs (SMAD6 or SMAD7). Read More

    Fibrodysplasia ossificans progressiva. A case report and focus on the BMP signaling pathway.
    Morphologie 2016 Dec 23;100(331):250-255. Epub 2016 May 23.
    Service de rhumatologie, CHU d'Angers, 49933 Angers cedex, France; GEROM groupe d'études remodelage osseux et biomatériaux, IRIS-IBS institut de biologie en santé, CHU d'Angers, université d'Angers, 49933 Angers cedex, France. Electronic address:
    Fibrodysplasia ossificans progressiva is a very rare heritable disease characterized by a progressive heterotopic endochondal ossification, occurring in the first decade of life, and leading thereafter to a severe ankylosis of the spine, limbs and jaw, with a progressive and severe functional disability. To date the cause of the disease remains unknown and no medical treatment has been proved efficient. It has recently been shown that a recurrent mutation in activation domain of the activin-receptor IA (ACVR1), a BMP receptor, could lead to an abnormal signalling pathway of BMP-4 and contribute to the occurrence of the devastating lesions characteristic of the disease. Read More

    Primum non nocere: a case of a humeral fracture in a patient with fibrodysplasia progressiva ossificans.
    Shoulder Elbow 2016 Jan 10;8(1):37-40. Epub 2015 Aug 10.
    The Shoulder Unit, Princess Elizabeth Orthopaedic Centre, Royal Devon and Exeter Hospital, Exeter, UK.
    Fibrodysplasia progressiva ossificans (FPO) is an extremely rare condition characterized by abnormal heterotopic bone formation. The condition is eponymously known as 'stoneman' disease because patients can become effectively entombed within abnormal heterotopic bone. We present the first known case of a diaphyseal humeral fracture managed conservatively in an adult patient with this condition. Read More

    Novel asymptomatic CNS findings in patients with ACVR1/ALK2 mutations causing fibrodysplasia ossificans progressiva.
    J Med Genet 2016 Dec 26;53(12):859-864. Epub 2016 Aug 26.
    Rare Disease Unit, Istituto Giannina Gaslini, Genoa, Italy.
    Background: Fibrodysplasia ossificans progressiva is an autosomal dominant disorder due to germline mutations of ACVR1/ALK2 causing progressive heterotopic endochondral ossifications. Evidence of central nervous system involvement has emerged only recently.

    Methods: We performed an observational cross-sectional brain MRI study in 13 patients (8 females, mean age 20 years), examining the relationship of clinical and neuroradiological findings. Read More

    The ACVR1 R206H mutation found in fibrodysplasia ossificans progressiva increases human induced pluripotent stem cell-derived endothelial cell formation and collagen production through BMP-mediated SMAD1/5/8 signaling.
    Stem Cell Res Ther 2016 Aug 17;7(1):115. Epub 2016 Aug 17.
    Institute for Human Genetics and the Division of Endocrinology and Metabolism, University of California, 513 Parnassus Avenue, HSE901G, San Francisco, CA, 94143-0794, USA.
    Background: The Activin A and bone morphogenetic protein (BMP) pathways are critical regulators of the immune system and of bone formation. Inappropriate activation of these pathways, as in conditions of congenital heterotopic ossification, are thought to activate an osteogenic program in endothelial cells. However, if and how this occurs in human endothelial cells remains unclear. Read More

    Total Ankylosis of the Upper Left Limb: A Case of Progressive Osseous Heteroplasia.
    Arch Bone Jt Surg 2016 Jun;4(3):285-8
    Orthopedic Research Center, Shahid Kamyab Hospital, Nakhrisi Junc, Fadaeian Islam St, Mashhad, Iran.
    Progressive osseous heteroplasia is a rare inherited disease that begins with skin ossification and proceeds into the deeper connective tissues. The disease should be distinguished from other genetic disorders of heterotopic ossification including fibrodysplasia ossificans progressiva (FOP) and Albright hereditary osteodystrophy (AHO). We report a case of progressive osseous heteroplasia in a twenty four years old male with a complaint of ankylosis of the entire upper left limb and digital cutaneous lesions and sparing of the other limbs and the axial skeleton. Read More

    ACVR1-Fc suppresses BMP signaling and chondro-osseous differentiation in an in vitro model of Fibrodysplasia ossificans progressiva.
    Bone 2016 Nov 2;92:29-36. Epub 2016 Aug 2.
    Department of Endocrinology and Metabolism, Tongji Hospital, Tongji University School of Medicine Shanghai, China. Electronic address:
    Fibrodysplasia ossificans progressiva (FOP) is a rare and devastating genetic disease of heterotopic endochondral ossification (HEO), and currently no effective therapies are available for this disease. A recurrent causative heterozygous mutation (c.617 G>A; R206H) for FOP was identified in activin receptor type IA (ACVR1), a bone morphogenetic protein (BMP) type I receptor. Read More

    Characteristic calcaneal ossification: an additional early radiographic finding in infants with fibrodysplasia ossificans progressiva.
    Pediatr Radiol 2016 Oct 4;46(11):1568-72. Epub 2016 Aug 4.
    Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
    Background: We have clinically encountered children with fibrodysplasia ossificans progressiva who had abnormal calcaneal ossification.

    Objective: To evaluate whether calcaneal ossification variants are significant radiographic findings in children with fibrodysplasia ossificans progressiva.

    Materials And Methods: Lateral feet radiographs in nine children who fulfilled the diagnostic criteria of fibrodysplasia ossificans progressiva were reviewed. Read More

    Inhibitors of the bone morphogenetic protein (BMP) signaling pathway: a patent review (2008-2015).
    Expert Opin Ther Pat 2016 Aug 4:1-14. Epub 2016 Aug 4.
    a Department of Pharmaceutical Sciences, College of Pharmacy , University of Nebraska Medical Center , Omaha , NE , USA.
    Introduction: The bone morphogenetic protein (BMP) is a critical signaling pathway and plays a diverse role in embryonic pattern formation and is implicated in a variety of disease processes, including anemia, bone formation, atherosclerosis, skin diseases, and cancers, among others.

    Areas Covered: This review covers small molecule inhibitors/antagonists of BMP in patent applications between 2008 - 2015, along with brief synopses of the disclosed inhibitors in the primary literature.

    Expert Opinion: The development of potent and selective BMP inhibitors is ongoing with most of the work centered around improving the selectivity and pharmacokinetic profile. Read More

    Pediatric Fibroblastic and Myofibroblastic Tumors: A Pictorial Review.
    Radiographics 2016 Jul-Aug;36(4):1195-214
    From the Mallinckrodt Institute of Radiology (K.M.S., E.F.S., G.K.) and Department of Pathology (A.S., J.A.C.), Washington University School of Medicine, 510 S Kingshighway Blvd, Campus Box 8131-MIR, St Louis, MO 63110.
    Pediatric fibroblastic and myofibroblastic tumors are a relatively common group of soft-tissue proliferations that are associated with a wide spectrum of clinical behavior. These tumors have been divided into the following categories on the basis of their biologic behavior: benign (eg, myositis ossificans, myofibroma, fibromatosis colli), intermediate-locally aggressive (eg, lipofibromatosis, desmoid fibroma), intermediate-rarely metastasizing (eg, inflammatory myofibroblastic tumors, infantile fibrosarcoma, low-grade myofibroblastic sarcoma), and malignant (eg, fibromyxoid sarcoma, adult fibrosarcoma). Imaging has a key role in the evaluation of lesion origin, extent, and involvement with adjacent structures, and in the treatment management and postresection surveillance of these tumors. Read More

    Generation of integration free induced pluripotent stem cells from fibrodysplasia ossificans progressiva (FOP) patients from urine samples.
    Stem Cell Res 2016 Jan 1;16(1):54-8. Epub 2015 Dec 1.
    Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Föhrer Strasse 15, 13353 Berlin, Germany; Berlin Institute of Health-Stem Cell Core Facility, Berlin, Germany.
    Fibrodysplasia ossificans progressiva (FOP) is an extremely rare, autosomal dominant transmitted genetic disease. Patients experience progressive bone formation replacing tendons, ligaments, muscle and soft tissue. Cause of FOP are gain-of-function mutations in the Bone Morphogenetic Protein (BMP) receptor Activin A receptor type 1 (ACVR1) (Kaplan et al. Read More

    The stone women-Myositis ossificans Progressiva.
    J Orthop Case Rep 2015 Oct-Dec;5(4):10-3
    Department Of Orthopaedics, Sri Ramachandra Medical College, Porur, Chennai - 600116. India.
    Introduction: Myositis ossificans progressiva is very rare with a worldwide prevalence of approximately 1 case in 2 million individuals. No ethnic, racial, or geographic predisposition has been described. Although familial forms inherited on a dominant autosomal basis have been described, most cases are sporadic. Read More

    Concurrent progress of reprogramming and gene correction to overcome therapeutic limitation of mutant ALK2-iPSC.
    Exp Mol Med 2016 Jun 3;48(6):e237. Epub 2016 Jun 3.
    Medical Research Division, Korea Institute of Oriental Medicine, Yuseong-gu, Daejeon, South Korea.
    Fibrodysplasia ossificans progressiva (FOP) syndrome is caused by mutation of the gene ACVR1, encoding a constitutive active bone morphogenetic protein type I receptor (also called ALK2) to induce heterotopic ossification in the patient. To genetically correct it, we attempted to generate the mutant ALK2-iPSCs (mALK2-iPSCs) from FOP-human dermal fibroblasts. However, the mALK2 leads to inhibitory pluripotency maintenance, or impaired clonogenic potential after single-cell dissociation as an inevitable step, which applies gene-correction tools to induced pluripotent stem cells (iPSCs). Read More

    Temporomandibular joint ankylosis as part of the clinical spectrum of Carey-Fineman-Ziter syndrome?
    Am J Med Genet A 2016 Aug 27;170(8):2191-5. Epub 2016 May 27.
    Department of Pediatric, Pediatric Genetic Unit, MBBM Foundation A.O.S. Gerardo, Monza, Italy.
    The Carey-Finema-Ziter syndrome (CFZS, MIM 254940) is an apparently autosomal recessively inherited disorder consisting of the combination of non-progressive congenital myopathy with Moebius and Pierre Robin sequence, facial anomalies and growth delay. Mental development has been described as normal or delayed. Temporomandibular joint (TMJ) ankylosis is the immobility of the joint caused by ankylotic fusion of the mandible to the cranial base or zygoma. Read More

    A novel ACVR1 mutation detected by whole exome sequencing in a family with an unusual skeletal dysplasia.
    Eur J Med Genet 2016 Jun 13;59(6-7):330-6. Epub 2016 May 13.
    Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran; Comprehensive Genetic Center, Hope Generation Foundation, Tehran, Iran; Gene Clinic, Tehran, Iran. Electronic address:
    "Disorganized Development of Skeletal Component" (DDSC) is a group of genetic skeletal dysplasia, caused by mutations in 9 genes including ACVR1. The most known ACVR1-related disorder is fibrodysplasia ossificans progressiva (FOP). FOP variants are frequently encountered with diagnostic challenges due to overlapping clinical manifestations and variable severity. Read More

    High-throughput screening for modulators of ACVR1 transcription: discovery of potential therapeutics for fibrodysplasia ossificans progressiva.
    Dis Model Mech 2016 Jun 28;9(6):685-96. Epub 2016 Apr 28.
    Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health and CEBR, Università degli Studi di Genova, Genova 16132, Italy Medical Genetics Unit, IRCCS Istituto Giannina Gaslini, Genova 16147, Italy
    The ACVR1 gene encodes a type I receptor of bone morphogenetic proteins (BMPs). Activating mutations in ACVR1 are responsible for fibrodysplasia ossificans progressiva (FOP), a rare disease characterized by congenital toe malformation and progressive heterotopic endochondral ossification leading to severe and cumulative disability. Until now, no therapy has been available to prevent soft-tissue swelling (flare-ups) that trigger the ossification process. Read More

    [Fibrodysplasia ossificans progressiva and osteoimmunology].
    Clin Calcium 2016 May;26(5):691-8
    Division of Pathophysiology, Research Center for Genomic Medicine, Saitama Medical University, Japan.
    Fibrodysplasia ossificans progressive (FOP) is a genetic disorder characterized by progressive heterotopic ossification (HO) in skeletal muscle, tendons and ligaments. FOP is caused by gain-of-function mutations of ALK2, a receptor of bone morphogenetic proteins. Immune responses have been suggested to be involved in HO in FOP, because muscle trauma induces acute HO in patients with FOP. Read More

    Cellular Hypoxia Promotes Heterotopic Ossification by Amplifying BMP Signaling.
    J Bone Miner Res 2016 Sep 20;31(9):1652-65. Epub 2016 Apr 20.
    Department of Orthopaedic Surgery, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA, USA.
    Hypoxia and inflammation are implicated in the episodic induction of heterotopic endochondral ossification (HEO); however, the molecular mechanisms are unknown. HIF-1α integrates the cellular response to both hypoxia and inflammation and is a prime candidate for regulating HEO. We investigated the role of hypoxia and HIF-1α in fibrodysplasia ossificans progressiva (FOP), the most catastrophic form of HEO in humans. Read More

    The Natural History of Flare-Ups in Fibrodysplasia Ossificans Progressiva (FOP): A Comprehensive Global Assessment.
    J Bone Miner Res 2016 Mar 14;31(3):650-6. Epub 2015 Nov 14.
    Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
    Fibrodysplasia ossificans progressiva (FOP) leads to disabling heterotopic ossification (HO) from episodic flare-ups. However, the natural history of FOP flare-ups is poorly understood. A 78-question survey on FOP flare-ups, translated into 15 languages, was sent to 685 classically-affected patients in 45 countries (six continents). Read More

    Fibrodysplasia ossificans progressiva: initial presentation with a preosseous lesion of the scalp and its MRI appearance.
    Skeletal Radiol 2016 Jul 22;45(7):991-6. Epub 2016 Mar 22.
    Department of Medical Imaging, Chi Mei Medical Center, Tainan, Taiwan.
    This case subject is a 1-year-old girl presenting with recurrent diffuse soft-tissue swelling of the scalp and periorbital region. Her family denied any known history of trauma. There was no obvious discoloration or local heat at the lesion. Read More

    Nanogel-Mediated RNAi Against Runx2 and Osx Inhibits Osteogenic Differentiation in Constitutively Active BMPR1A Osteoblasts.
    ACS Biomater Sci Eng 2015 Nov 25;1(11):1139-1150. Epub 2015 Sep 25.
    Department of Biomedical Engineering, Carnegie Mellon University, 700 Technology Drive, Pittsburgh, Pennsylvania 15219, United States.
    Trauma-induced heterotopic ossification (HO) and fibrodysplasia ossificans progressiva (FOP) are acquired and genetic variants of pathological bone formation occurring in soft tissues. Conventional treatment modalities target the inflammatory processes preceding bone formation. We investigated the development of a prophylaxis for heterotopic bone formation by addressing the biological basis for HO - dysregulation in the bone morphogenetic protein (BMP) signaling pathway. Read More

    Palovarotene Inhibits Heterotopic Ossification and Maintains Limb Mobility and Growth in Mice With the Human ACVR1(R206H) Fibrodysplasia Ossificans Progressiva (FOP) Mutation.
    J Bone Miner Res 2016 Sep 12;31(9):1666-75. Epub 2016 Mar 12.
    Department of Orthopedic Surgery, Perelman School of Medicine, the University of Pennsylvania, Philadelphia, PA, USA.
    Fibrodysplasia ossificans progressiva (FOP), a rare and as yet untreatable genetic disorder of progressive extraskeletal ossification, is the most disabling form of heterotopic ossification (HO) in humans and causes skeletal deformities, movement impairment, and premature death. Most FOP patients carry an activating mutation in a bone morphogenetic protein (BMP) type I receptor gene, ACVR1(R206H) , that promotes ectopic chondrogenesis and osteogenesis and, in turn, HO. We showed previously that the retinoic acid receptor γ (RARγ) agonist palovarotene effectively inhibited HO in injury-induced and genetic mouse models of the disease. Read More

    Effectiveness and mode of action of a combination therapy for heterotopic ossification with a retinoid agonist and an anti-inflammatory agent.
    Bone 2016 Sep 15;90:59-68. Epub 2016 Feb 15.
    Translational Research Program in Pediatric Orthopaedics, Division of Orthopaedic Surgery, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA. Electronic address:
    Heterotopic ossification (HO) consists of ectopic cartilage and bone formation following severe trauma or invasive surgeries, and a genetic form of it characterizes patients with Fibrodysplasia Ossificans Progressiva (FOP). Recent mouse studies showed that HO was significantly inhibited by systemic treatment with a corticosteroid or the retinoic acid receptor γ agonist Palovarotene. Because these drugs act differently, the data raised intriguing questions including whether the drugs affected HO via similar means, whether a combination therapy would be more effective or whether the drugs may hamper each other's action. Read More

    Fibrodysplasia Ossificans Progressiva.
    J Coll Physicians Surg Pak 2016 Feb;26(2):154-5
    Department of Pediatric Medicine, Children Hospital and Institute of Child Health, Lahore.
    Fibrodysplasia Ossificans Progressiva (FOP) is a rare autosomal dominant disorder characterized by postnatal progressive heterotopic ossification of connective tissue and congenital malformation of big toes. We report a 3-year male toddler with clinical and radiological features of FOP. He was born with bilateral hallux valgus and at the age of 3 years presented with hard swellings over back, scapular region and forehead that were initially inflammatory and then became bony hard. Read More

    The Diversity of the Clinical Phenotypes in Patients With Fibrodysplasia Ossificans Progressiva.
    J Clin Med Res 2016 Mar 26;8(3):246-53. Epub 2016 Jan 26.
    Institute of Medical Chemistry, Medical University of Vienna, Austria.
    Background: The clinical presentation, phenotypic characterization and natural history of fibrodysplasia ossificans progressiva (FOP) are diverse and the natural history of the disease is, to a certain extent, different from one patient to another.

    Methods: In a series of 11 patients (eight girls and three boys, aged 0 - 16 years), variable clinical presentations were the landmarks of these patients. At birth, all of our patients manifested short great toes in a valgus position. Read More

    Common mutations in ALK2/ACVR1, a multi-faceted receptor, have roles in distinct pediatric musculoskeletal and neural orphan disorders.
    Cytokine Growth Factor Rev 2016 Feb 28;27:93-104. Epub 2015 Dec 28.
    Departments of Orthopaedic Surgery and Genetics, and the Center for Research in FOP and Related Disorders, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104 United States. Electronic address:
    Activin receptor-like kinase-2 (ALK2), the product of ACVR1, is a member of the type I bone morphogenetic protein (BMP) receptor family. ALK2 exerts key and non-redundant roles in numerous developmental processes, including the specification, growth and morphogenesis of endochondral skeletal elements. There is also strong evidence that BMP signaling plays important roles in determination, differentiation and function of neural cells and tissues. Read More

    Inhibition of TGFβ signaling decreases osteogenic differentiation of fibrodysplasia ossificans progressiva fibroblasts in a novel in vitro model of the disease.
    Bone 2016 Mar 6;84:169-80. Epub 2016 Jan 6.
    Department of Clinical Chemistry, VU University Medical Center, MOVE Research Institute, Amsterdam, The Netherlands. Electronic address:
    Fibrodysplasia ossificans progressiva is a rare genetic disorder characterized by progressive heterotopic ossification. FOP patients develop soft tissue lumps as a result of inflammation-induced flare-ups which leads to the irreversible replacement of skeletal muscle tissue with bone tissue. Classical FOP patients possess a mutation (c. Read More

    Granting immunity to FOP and catching heterotopic ossification in the Act.
    Semin Cell Dev Biol 2016 Jan 17;49:30-6. Epub 2015 Dec 17.
    The Department of Orthopaedic Surgery, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA; The Department of Genetics, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA; The Center for Research in FOP & Related Disorders, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:
    The progressive transformation of one organ system into another is a fundamental signature of fibrodysplasia ossificans progressiva (FOP), the most catastrophic form of extraskeletal bone formation in humans. In all affected individuals, FOP is caused by heterozygous missense gain-of-function mutations in Activin receptor A type I (ACVR1), a bone morphogenetic protein (BMP) type I receptor. Loss of autoinhibition of the mutant receptor (mACVR1) results in dysregulated BMP pathway signaling, and is necessary for the myriad developmental features of FOP, but does not appear sufficient to induce the episodic flare-ups that lead to disabling post-natal heterotopic endochondral ossification (HEO) and that are a hallmark of the disease. Read More

    Development of New Therapeutic Agents for Fibrodysplasia Ossificans Progressiva.
    Curr Mol Med 2016 ;16(1):4-11
    College of Veterinary Medicine, Western University of Health Sciences, Pomona, CA 91766, USA.
    Fibrodysplasia ossificans progressiva (FOP, MIM #135100) is a rare genetic disorder of heterotopic endochondral ossification, resulting in transformation of soft tissue into episodic bone formation. Currently, no effective treatment for FOP has been established. The causative heterozygous genetic mutations have been identified in either the intracellular glycine-serine-rich (GS) domain or kinase domain of ALK2 (Activin-like kinase-2, also known as Activin A receptor type I, ACVR1), a type I receptor of bone morphogenetic proteins (BMP). Read More

    Structural insights into BMP receptors: Specificity, activation and inhibition.
    Cytokine Growth Factor Rev 2016 Feb 24;27:13-34. Epub 2015 Nov 24.
    Molecular Plant Physiology and Biophysics, Julius-von-Sachs-Institute of the University Wuerzburg, Julius-von-Sachs-Platz 2, D-97082 Wuerzburg, Germany. Electronic address:
    Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-β family (TGFβ), which signal through hetero-tetrameric complexes of type I and type II receptors. In humans there are many more TGFβ ligands than receptors, leading to the question of how particular ligands can initiate specific signaling responses. Here we review structural features of the ligands and receptors that contribute to this specificity. Read More

    Signal Transduction: Gain of Activin Turns Muscle into Bone.
    Curr Biol 2015 Dec;25(23):R1136-8
    Department of Molecular Cell Biology, Cancer Genomics Centre Netherlands, Leiden University Medical Center, The Netherlands. Electronic address:
    Recent data provide an unexpected twist in our understanding of the pathogenesis of fibrodysplasia ossificans progressiva. Surprisingly, the causative amino acid mutation of the BMP receptor responds to activin, thereby turning soft tissues into bone. Read More

    A Door Opens for Fibrodysplasia Ossificans Progressiva.
    Trends Biochem Sci 2016 Feb 1;41(2):119-21. Epub 2015 Dec 1.
    Division of Pathophysiology, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama 350-1241, Japan. Electronic address:
    Fibrodysplasia ossificans progressiva (FOP), characterized by extra bone formation in soft tissues, is caused by a gain-of-function mutation in ACVR1, a transmembrane receptor. Recently, a potential treatment was developed by identifying a novel molecular mechanism underlying bone formation in FOP. These findings have opened the door to beating FOP. Read More

    Induced Pluripotent Stem Cells to Model Human Fibrodysplasia Ossificans Progressiva.
    Stem Cell Reports 2015 Dec 26;5(6):963-70. Epub 2015 Nov 26.
    Department of Molecular Cell Biology, Cancer Genomics Centre Netherlands, Leiden University Medical Center, Leiden 2300, the Netherlands. Electronic address:
    Fibrodysplasia ossificans progressiva (FOP) is a rare disease characterized by progressive ossification of soft tissues, for which there is no effective treatment. Mutations in the bone morphogenetic protein (BMP) type I receptor activin receptor-like kinase 2 (ACVR1/ALK2) are the main cause of FOP. We generated human induced pluripotent stem cells (hiPSCs) from FOP patients with the ALK2 R206H mutation. Read More

    Neofunction of ACVR1 in fibrodysplasia ossificans progressiva.
    Proc Natl Acad Sci U S A 2015 Dec 30;112(50):15438-43. Epub 2015 Nov 30.
    Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto, 606-8507, Japan; Department of Tissue Regeneration, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, 606-8507, Japan; Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan
    Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease characterized by extraskeletal bone formation through endochondral ossification. FOP patients harbor point mutations in ACVR1 (also known as ALK2), a type I receptor for bone morphogenetic protein (BMP). Two mechanisms of mutated ACVR1 (FOP-ACVR1) have been proposed: ligand-independent constitutive activity and ligand-dependent hyperactivity in BMP signaling. Read More

    Quality of life of patients with fibrodysplasia ossificans progressiva.
    J Child Orthop 2015 Dec 13;9(6):489-93. Epub 2015 Nov 13.
    Hospital Regional de Alta Especialidad del Bajio, Boulevard Milenio No. 130, Col. San Carlos la Roncha, C.P. 37660, León, Guanajuato, Mexico.
    Introduction: Fibrodysplasia ossificans progressiva (FOP) is a rare disorder characterized by episodes of acute pain and heterotopic ossification of soft tissue, and progressively limited physical function and social participation.

    Objective: We aimed to determine the impact of FOP on quality of life, specifying areas or dimensions most affected.

    Materials And Methods: This was a transverse observational study; patients with FOP were assessed using the Short Form 36. Read More

    Clinical and Genetic Analysis of Fibrodysplasia Ossificans Progressiva: A Case Report and Literature Review.
    J Clin Diagn Res 2015 Aug 1;9(8):RD01-3. Epub 2015 Aug 1.
    Research Associate, Diagnostics Division, Centre for DNA Fingerprinting and Diagnostics , Hyderabad, India .
    Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder characterized by congenital malformation of the great toes and disabling heterotopic ossification in specific anatomic locations with a world wide prevalence of 1 in 2 million population. Nearly 90% of patients with FOP are misdiagnosed and mismanaged. We present a case of a four-year-old boy brought by his parents with the complaints of stiffness of right shoulder, neck and multiple swellings over the upper back noted over the past 4 months. Read More

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