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    3170 results match your criteria Osteopetrosis

    1 OF 64

    Carbonic anhydrase II deficiency: report of a novel mutation.
    CEN Case Rep 2016 May 8;5(1):108-112. Epub 2015 Dec 8.
    Department of Medicine (38), College of Medicine, King Saud University, P.O. Box 2925, Riyadh, 11461, Kingdom of Saudi Arabia.
    Carbonic anhydrase II (CAII) deficiency is an autosomal recessive disorder characterized by renal tubular acidosis, osteopetrosis, recurrent bone fractures, renal stones, growth failure, and mental retardation. Several cases have been reported in Saudi Arabia with homozygous mutations in CA2 consistent with a high degree of consanguinity. We report a case of carbonic anhydrase II deficiency with short stature, mixed renal tubular acidosis, recurrent bone fractures due to trivial trauma, recurrent renal stones and cerebral calcification. Read More

    Periodontal profile and radiographic characterization of the jaws in a patient with autosomal dominant osteopetrosis.
    Endocrinol Diabetes Metab Case Rep 2017 21;2017. Epub 2017 Apr 21.
    Department of Internal Medicine and Endocrine Section, Medical School and Hospital Universitário Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de JaneiroBrazil.
    Osteopetrosis (OP) comprehends a rare group of conditions, presenting on radiographs increased bone density, deriving from irregularities in osteoclast differentiation or function. In the autosomal dominant osteopetrosis (ADO), some patients stay asymptomatic for some time, or only develop mild symptoms. The dental surgeon is often the first to presuppose the disease during routine imaging examinations, referring the patient to a specialized medical group. Read More

    Genetic disorders in beef cattle: a review.
    Genes Genomics 2017 3;39(5):461-471. Epub 2017 Mar 3.
    Department of Animal Improvement, Institute of Genetics and Animal Breeding, Polish Academy of Sciences, Postępu 36A, Jastrzębiec, 05-552 Magdalenka, Poland.
    The main purpose of present review is to describe and organize autosomal recessive disorders (arachnomelia, syndactylism, osteopetrosis, dwarfism, crooked tail syndrome, muscular hyperplasia, glycogen storage disease, protoporphyria), which occur among beef cattle, and methods that can be applied to detect these defects. Prevalence of adverse alleles in beef breeds happens due to human activity-selections of favorable features, e.g. Read More

    Use of an Industrial Tungsten Carbide Drill in the Treatment of a Complex Fracture in a Patient with Severe Osteopetrosis: A Case Report.
    Malays Orthop J 2017 Mar;11(1):64-67
    Department of Orthopaedics, Tan Tock Seng Hospital, Singapore.
    The treatment of fractures in osteopetrosis can be complicated and difficult. We describe the use of an industrial grade tungsten carbide drill bit in the treatment of one of these complex fractures. An industrial grade tungsten carbide drill bit was used to fashion a medullary canal in the surgical treatment of a left peri-implant fracture of the neck of femur in a patient with osteopetrosis. Read More

    Disabling Osteopetrosis in an Young Lady.
    J Assoc Physicians India 2016 Dec;64(12):92-94
    Assistant Professor, Dept. of Medicine, Midnapore Medical College, Midnapore, West Bengal.
    Osteopetrosis is a rare disorder of osteoclastic bone resorption leading to hyperostosis. Albers-Schonberg disease, an autosomal dominant variant of osteopetrosis occurs in young adults and has a benign course. A 17 year old female presented with generalized weakness and pallor for last two months. Read More

    Traumatic multiple cervical spine injuries in a patient with osteopetrosis and its management.
    Eur Spine J 2017 Apr 9. Epub 2017 Apr 9.
    Spine Fellow, Lilavati Hospital and Research Centre, Bandra reclamation, Bandra west, Mumbai, Maharashtra, 400050, India.
    Study Design: Single case report.

    Objective/purpose: To report multiple level fractures of cervical spine in a patient with osteopetrosis and its management. Osteopetrosis is a rare inherited condition characterized by defective remodeling resulting in hard and brittle bones with diffuse osteosclerosis. Read More

    ClC Channels and Transporters: Structure, Physiological Functions, and Implications in Human Chloride Channelopathies.
    Front Pharmacol 2017 23;8:151. Epub 2017 Mar 23.
    Department of Physiology and Biophysics, Dalhousie University, Halifax NS, Canada.
    The discovery of ClC proteins at the beginning of the 1990s was important for the development of the Cl(-) transport research field. ClCs form a large family of proteins that mediate voltage-dependent transport of Cl(-) ions across cell membranes. They are expressed in both plasma and intracellular membranes of cells from almost all living organisms. Read More

    Autozygosity reveals recessive mutations and novel mechanisms in dominant genes: implications in variant interpretation.
    Genet Med 2017 Apr 6. Epub 2017 Apr 6.
    Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
    Purpose: The purpose of this study is to describe recessive alleles in strictly dominant genes. Identifying recessive mutations in genes for which only dominant disease or risk alleles have been reported can expand our understanding of the medical relevance of these genes both phenotypically and mechanistically. The Saudi population is enriched for autozygosity, which enhances the homozygous occurrence of alleles, including pathogenic alleles in genes that have been associated only with a dominant inheritance pattern. Read More

    Role and mechanism of action of leucine-rich repeat kinase 1 in bone.
    Bone Res 2017 14;5:17003. Epub 2017 Mar 14.
    Musculoskeletal Disease Center, Jerry L. Pettis Memorial VA Medical Center, Loma Linda, CA, USA; Department of Medicine, Loma Linda University, Loma Linda, CA, USA.
    Leucine-rich repeat kinase 1 (LRRK1) plays a critical role in regulating cytoskeletal organization, osteoclast activity, and bone resorption with little effect on bone formation parameters. Deficiency of Lrrk1 in mice causes a severe osteopetrosis in the metaphysis of the long bones and vertebrae bones, which makes LRRK1 an attractive alternative drug target for the treatment of osteoporosis and other high-turnover bone diseases. This review summarizes recent advances on the functions of the Lrrk1-related family members, Lrrk1 deficiency-induced skeletal phenotypes, LRRK1 structure-function, potential biological substrates and interacting proteins, and the mechanisms of LRRK1 action in osteoclasts. Read More

    V-ATPases Containing a3 Subunit Play a Direct Role in Enamel Development in Mice.
    J Cell Biochem 2017 Mar 11. Epub 2017 Mar 11.
    Faculty of Dentistry, Dental Research Institute, University of Toronto, Toronto, Ontario, Canada.
    Vacuolar H(+) -ATPases (V-ATPases) are ubiquitous multisubunit proton pumps responsible for organellar pH maintenance. Mutations in the a3 subunit of V-ATPases cause autosomal recessive osteopetrosis, a rare disease due to impaired bone resorption. Patients with osteopetrosis also display dental anomalies, such as enamel defects; however, it is not clear whether these enamel abnormalities are a direct consequence of the a3 mutations. Read More

    Case Report of Clinical Vignette: Osteopetrosis.
    Mil Med 2017 Mar;182(3):e1886-e1888
    Division of Endocrinology, Department of Medicine, Naval Medical Center San Diego, 34800 Bob Wilson Drive, San Diego, CA 92134-3300.
    Introduction: Osteopetrosis is a connective tissue disorder resulting from abnormally dense bone predisposing patients to fracture. The clinical pattern of fractures across time and space as well as suggestive radiographic findings usually raises diagnostic suspicion. Multiple genetic mutations resulting in dysfunctional osteoclasts have been implicated in the pathogenesis of osteopetrosis with variable inheritance patterns. Read More

    Immunoregulatory properties of the cytokine IL-34.
    Cell Mol Life Sci 2017 Mar 3. Epub 2017 Mar 3.
    INSERM UMR1064, Center for Research in Transplantation and Immunology-ITUN, Université de Nantes, 30 Bd. Jean Monnet, 44093, Nantes Cedex 01, France.
    Interleukin-34 is a cytokine with only partially understood functions, described for the first time in 2008. Although IL-34 shares very little homology with CSF-1 (CSF1, M-CSF), they share a common receptor CSF-1R (CSF-1R) and IL-34 has also two distinct receptors (PTP-ζ) and CD138 (syndecan-1). To make the situation more complex, IL-34 has also been shown as pairing with CSF-1 to form a heterodimer. Read More

    Autosomal recessive osteopetrosis with a unique imaging finding: multiple encephaloceles.
    Skeletal Radiol 2017 May 23;46(5):701-704. Epub 2017 Feb 23.
    Department of Pediatrics, School of Medicine, Ondokuz Mayıs University, Kurupelit, Samsun, Turkey.
    Osteopetrosis is a hereditary form of sclerosing bone dysplasia with various radiological and clinical presentations. The autosomal recessive type, also known as malignant osteopetrosis, is the most severe type, with the early onset of manifestations. A 5-month-old infant was admitted to our hospital with recurrent respiratory tract infections. Read More

    Surface microtopography modulates sealing zone development in osteoclasts cultured on bone.
    J R Soc Interface 2017 Feb;14(127)
    Department of Molecular Cell Biology, Weizmann Institute of Science, Wolfson Building for Biological Research, Room 618, 234 Herzl Street, 7610001 Rehovot, Israel
    Bone homeostasis is continuously regulated by the coordinated action of bone-resorbing osteoclasts and bone-forming osteoblasts. Imbalance between these two cell populations leads to pathological bone diseases such as osteoporosis and osteopetrosis. Osteoclast functionality relies on the formation of sealing zone (SZ) rings that define the resorption lacuna. Read More

    A paradoxical presentation of rickets and secondary osteomyelitis of the jaw in Type II autosomal dominant osteopetrosis: Rare case reports.
    Indian J Dent Res 2016 Nov-Dec;27(6):667-671
    Department of Oral Medicine and Radiology, Tamil Nadu Government Dental College and Hospital, Chennai, Tamil Nadu, India.
    Osteopetrosis is a rare genetic bone disorder arising due to a defect in the differentiation or function of osteoclast which results in a generalized increase in bone mass. Osteomyelitis is one of the most common complications because of decreased bone marrow function and compromised blood supply. Radiologist plays a vital role in diagnosing osteopetrosis. Read More

    Osteopetroses, emphasizing potential approaches to treatment.
    Bone 2017 Feb 4. Epub 2017 Feb 4.
    Department of Medicine, Indiana University, 1120 W. Michigan St., Indianapolis, IN 46202, USA; Department of Medical and Molecular Genetics, Indiana University, 1120 W. Michigan St., Indianapolis, IN 46202, USA. Electronic address:
    Osteopetroses are a heterogeneous group of rare genetic bone diseases sharing the common hallmarks of reduced osteoclast activity, increased bone mass and high bone fragility. Osteoclasts are bone resorbing cells that contribute to bone growth and renewal through the erosion of the mineralized matrix. Alongside the bone forming activity by osteoblasts, osteoclasts allow the skeleton to grow harmonically and maintain a healthy balance between bone resorption and formation. Read More

    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

    Murine Rankl(-/-) Mesenchymal Stromal Cells Display an Osteogenic Differentiation Defect Improved by a RANKL-Expressing Lentiviral Vector.
    Stem Cells 2017 May 1;35(5):1365-1377. Epub 2017 Mar 1.
    Milan Unit, CNR-IRGB, Milan, Italy.
    Autosomal recessive osteopetrosis (ARO) is a severe bone disease characterized by increased bone density due to impairment in osteoclast resorptive function or differentiation. Hematopoietic stem cell transplantation is the only available treatment; however, this therapy is not effective in RANKL-dependent ARO, since in bone this gene is mainly expressed by cells of mesenchymal origin. Of note, whether lack of RANKL production might cause a defect also in the bone marrow (BM) stromal compartment, possibly contributing to the pathology, is unknown. Read More

    Hematopoietic stem cell transplantation corrects osteopetrosis in a child carrying a novel homozygous mutation in the FERMT3 gene.
    Bone 2017 Apr 14;97:126-129. Epub 2017 Jan 14.
    Humanitas Clinical and Research Institute, Rozzano, Italy; CNR-IRGB, Milan Unit, Milan, Italy.
    Osteopetrosis (OPT) is a rare skeletal disorder with phenotypic and genotypic heterogeneity: a variety of clinical features besides the bony defect may be present, and at least ten different genes are known to be involved in the disease pathogenesis. In the framework of this heterogeneity, we report the clinical description of a neonate, first child of consanguineous parents, who had osteoclast-rich osteopetrosis and bone marrow failure in early life, but no other usual classical features of infantile malignant OPT, such as visual or hearing impairments. Because of the severe presentation at birth, the patient received Hematopoietic Stem Cell Transplantation (HSCT) at 2months of age with successful outcome. Read More

    A Review of Selected Genes with Known Effects on Performance and Health of Cattle.
    Front Vet Sci 2016 15;3:113. Epub 2016 Dec 15.
    National Animal Disease Center, USDA, ARS , Ames, IA , USA.
    There are genetic conditions that influence production in dairy and beef cattle. The objective of this review was to describe relevant genetic conditions that have been associated with productivity and health in cattle. Genes or genomic regions that have been identified as a candidate for the condition will be included, and the genetic basis of the condition will be defined. Read More

    Clinical Characteristics and Treatment of Osteopetrosis Complicated by Osteomyelitis of the Mandible.
    J Craniofac Surg 2016 Nov;27(8):e728-e730
    Department of Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, Liaoning Institute of Dental Research, Heping District, Shenyang, China.
    Osteopetrosis represents a heterogeneous group of rare, hereditary bone disorders with variable clinical features, and an increase in bone density. Osteomyelitis of the jaws is a significant complication of osteopetrosis. In this article, a reported patient with osteopetrosis complicated by osteomyelitis of the mandible was examined. Read More

    Enhanced but hypofunctional osteoclastogenesis in an autosomal dominant osteopetrosis type II case carrying a c.1856C>T mutation in CLCN7.
    Bone Res 2016 29;4:16035. Epub 2016 Nov 29.
    Laboratory of Endocrinology and Metabolism, Department of Endocrinology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University , Chengdu, China.
    Type II autosomal dominant osteopetrosis (ADO2), which is the most common form of osteopetrosis, is caused by heterozygous mutations in the chloride channel 7 (CLCN7) gene. The osteopetrosis of ADO2 has been attributed to hypofunctional osteoclasts. The mechanism underlying the abnormality in osteoclast function remains largely unknown. Read More

    Can acetazolamide be used to treat diseases involving increased bone mineral density?
    Intractable Rare Dis Res 2016 Nov;5(4):284-289
    Paediatric Nephrology Unit, Department of Pediatrics, Nuestra Señora de Candelaria University Hospital, Tenerife, Spain.
    Sclerosing bone dysplasias are a series of clinically and genetically heterogeneous diseases characterized by functional failure of the osteoclasts in bone resorption, leading to an excessive amount of bone mineral density (BMD) which could have serious clinical consequences. We treated three children affected with seriously high levels of BMD with acetazolamide, with the intention of inducing metabolic acidosis, thus increasing bone resorption and reducing BMD. All our patients tolerated and followed the treatment well and the clinical response was satisfactory in all cases. Read More

    Biallelic Mutations in MITF Cause Coloboma, Osteopetrosis, Microphthalmia, Macrocephaly, Albinism, and Deafness.
    Am J Hum Genet 2016 Dec 23;99(6):1388-1394. Epub 2016 Nov 23.
    Ophthalmic Genetics and Visual Function Branch, National Eye Institute, NIH, Bethesda, MD 20892, USA; Children's National Medical Center, Washington, DC 20010, USA. Electronic address:
    Human MITF is, by convention, called the "microphthalmia-associated transcription factor" because of previously published seminal mouse genetic studies; however, mutations in MITF have never been associated with microphthalmia in humans. Here, we describe a syndrome that we term COMMAD, characterized by coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness. COMMAD is associated with biallelic MITF mutant alleles and hence suggests a role for MITF in regulating processes such as optic-fissure closure and bone development or homeostasis, which go beyond what is usually seen in individuals carrying monoallelic MITF mutations. Read More

    Debridement in chronic osteomyelitis with benign osteopetrosis: A case report.
    Exp Ther Med 2016 Nov 15;12(5):2811-2814. Epub 2016 Sep 15.
    Department of Otorhinolaryngology, Xiamen Chang Gung Hospital, Xiamen, Fujian 361000, P.R. China.
    Osteopetrosis is a rare bone disease caused by metabolic imbalances as a result of genetic mutations. For instance, autosomal dominant osteopetrosis is caused by a missense mutation of the C1CN7 gene. This was first reported in 1904 and is thought to be caused by osteoclastic dysfunction and an impaired bone resorption ability. Read More

    Raine Syndrome (OMIM #259775), Caused By FAM20C Mutation, Is Congenital Sclerosing Osteomalacia With Cerebral Calcification (OMIM 259660).
    J Bone Miner Res 2017 Apr 14;32(4):757-769. Epub 2016 Dec 14.
    Center for Metabolic Bone Disease and Molecular Research, Shriners Hospital for Children, St. Louis, MO, USA.
    In 1985, we briefly reported infant sisters with a unique, lethal, autosomal recessive disorder designated congenital sclerosing osteomalacia with cerebral calcification. In 1986, this condition was entered into Mendelian Inheritance In Man (MIM) as osteomalacia, sclerosing, with cerebral calcification (MIM 259660). However, no attestations followed. Read More

    Dental care approach in patients with osteopetrosis.
    Eur Arch Paediatr Dent 2016 Dec 17;17(6):435-443. Epub 2016 Nov 17.
    Dept of Oral Health Sciences-Orthodontics, University Hospitals Leuven, KU Leuven and Dentistry, Kapucijnenvoer 7, 3000, Louvain, Belgium.
    Aim: To describe dental and dentofacial characteristics observed in patients diagnosed with osteopetrosis and to advise a dental care approach in these patients.

    Methods: Four patients were clinically diagnosed with osteopetrosis, characterised by increased bone density, bone marrow failure, blindness and deafness due to compression of cranial nerves. All patients were dentally screened at different ages (2. Read More

    [Diagnosis, evolution and prognosis of prenatally diagnosed suprasellar cysts].
    Neurochirurgie 2016 Dec 14;62(6):300-305. Epub 2016 Nov 14.
    Service de neurochirurgie pédiatrique, hôpital Necker-Enfants-Malades, AP-HP, 149, rue de Sèvres, 75743 Paris cedex 15, France.
    Suprasellar arachnoid cysts (SAC) in children are considered rare, but the incidence is increasing due to the improvement of prenatal diagnosis. We present 15 cases of SAC diagnosed during the antenatal period between 2005 and 2015. The records were reviewed retrospectively by specifying the radiological characteristics, treatment modalities, outcomes, and long-term monitoring. Read More

    Proximal femoral fracture surgery in a patient with osteopetrosis tarda: complications and treatment strategy.
    Int Med Case Rep J 2016 1;9:347-351. Epub 2016 Nov 1.
    Department of Trauma and Orthopedics, Adana Numune Training and Educational Hospital, Adana, Turkey.
    Osteopetrosis is a rare, inherited disease characterized by defects in osteoclastic function that results in defective bone resorption. When fractures are encountered, fixation is extremely difficult. Osteopetrosis patients have an increased predisposition to infection. Read More

    Homozygous deletion of RAG1, RAG2 and 5' region TRAF6 causes severe immune suppression and atypical osteopetrosis.
    Clin Genet 2017 Jun 19;91(6):902-907. Epub 2017 Mar 19.
    Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
    Mutations of several genes have been implicated in autosomal recessive osteopetrosis (OP), a disease caused by impaired function and differentiation of osteoclasts. Severe combined immune deficiencies (SCID) can likewise result from different genetic mutations. We report two siblings with SCID and an atypical phenotype of OP. Read More

    Phenotypic severity of autosomal dominant osteopetrosis type II (ADO2) mice on different genetic backgrounds recapitulates the features of human disease.
    Bone 2017 Jan 14;94:34-41. Epub 2016 Oct 14.
    Medicine, Indiana University School of Medicine, IN, USA; Medical and Molecular Genetics, Indiana University School of Medicine, IN, USA.
    Autosomal dominant osteopetrosis type II (ADO2) is a heritable osteosclerotic bone disorder due to dysfunctional osteoclast activity. ADO2 is caused by missense mutations in the chloride channel 7 (CLCN7) gene characterized by osteosclerosis with multiple fractures. ADO2 can result in osteomyelitis, visual loss and bone marrow failure. Read More

    Review of the recombinant human interferon gamma as an immunotherapeutic: Impacts of production platforms and glycosylation.
    J Biotechnol 2016 Dec 27;240:48-60. Epub 2016 Oct 27.
    College of Science and Engineering, James Cook University, Townsville 4811, Queensland, Australia; Centre for Biodiscovery and Molecular Development of Therapeutics, James Cook University, Townsville 4811, Queensland, Australia. Electronic address:
    Human interferon gamma is a cytokine belonging to a diverse group of interferons which have a crucial immunological function against mycobacteria and a wide variety of viral infections. To date, it has been approved for treatment of chronic granulomatous disease and malignant osteopetrosis, and its application as an immunotherapeutic agent against cancer is an increasing prospect. Recombinant human interferon gamma, as a lucrative biopharmaceutical, has been engineered in different expression systems including prokaryotic, protozoan, fungal (yeasts), plant, insect and mammalian cells. Read More

    PLEKHM1/DEF8/RAB7 complex regulates lysosome positioning and bone homeostasis.
    JCI Insight 2016 Oct 20;1(17):e86330. Epub 2016 Oct 20.
    Center for Osteoporosis and Metabolic Bone Diseases, Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.; Department of Physiology and Biophysics, and.
    Mutations of the Plekhm1 gene in humans and rats cause osteopetrosis, an inherited bone disease characterized by diminished bone resorption by osteoclasts. PLEKHM1 binds to RAB7 and is critical for lysosome trafficking. However, the molecular mechanisms by which PLEKHM1 regulates lysosomal pathways remain unknown. Read More

    Dendritic Cell-Specific Transmembrane Protein (DC-STAMP) Regulates Osteoclast Differentiation via the Ca(2+) /NFATc1 Axis.
    J Cell Physiol 2017 Sep 12;232(9):2538-2549. Epub 2017 Apr 12.
    Division of Allergy/Immunology and Rheumatology, The University of Rochester, Rochester, New York.
    DC-STAMP is a multi-pass transmembrane protein essential for cell-cell fusion between osteoclast precursors during osteoclast (OC) development. DC-STAMP-/- mice have mild osteopetrosis and form mononuclear cells with limited resorption capacity. The identification of an Immunoreceptor Tyrosine-based Inhibitory Motif (ITIM) on the cytoplasmic tail of DC-STAMP suggested a potential signaling function. Read More

    How rare bone diseases have informed our knowledge of complex diseases.
    Bonekey Rep 2016 21;5:839. Epub 2016 Sep 21.
    Department of Oral and Craniofacial Sciences, University of Missouri-Kansas City School of Dentistry , Kansas City, MO, USA.
    Rare bone diseases, generally defined as monogenic traits with either autosomal recessive or dominant patterns of inheritance, have provided a rich database of genes and associated pathways over the past 2-3 decades. The molecular genetic dissection of these bone diseases has yielded some major surprises in terms of the causal genes and/or involved pathways. The discovery of genes/pathways involved in diseases such as osteopetrosis, osteosclerosis, osteogenesis imperfecta and many other rare bone diseases have all accelerated our understanding of complex traits. Read More

    Osteopetrosis in a neonatal donkey.
    Aust Vet J 2016 Oct;94(10):358-61
    Faculty of Veterinary Science, University of Melbourne, Melbourne, Victoria, Australia.
    Osteopetrosis is a rare disorder characterised by a defect in osteoclastic bone resorption. This report describes osteopetrosis in a neonatal donkey that suffered a displaced tibial fracture. Radiographic examination identified generalised reduction in medullary cavity size, thickened mid-diaphyseal cortices and conical metaphyseal bone extending toward the mid-diaphysis of long bones. Read More


    Leucine-rich repeat kinase-1 regulates osteoclast function by modulating RAC1/Cdc42 Small GTPase phosphorylation and activation.
    Am J Physiol Endocrinol Metab 2016 Oct 6;311(4):E772-E780. Epub 2016 Sep 6.
    Musculoskeletal Disease Center, Jerry L. Pettis Memorial Veterans Affairs Medical Center, Loma Linda, California; Department of Medicine, Loma Linda University, Loma Linda, California;
    Leucine-rich repeat kinase-1 (Lrrk1) consists of ankyrin repeats (ANK), leucine-rich repeats (LRR), a GTPase-like domain of Roc (ROC), a COR domain, a serine/threonine kinase domain (KD), and WD40 repeats (WD40). Previous studies have revealed that knockout (KO) of Lrrk1 in mice causes severe osteopetrosis, and a human mutation of Lrrk1 leads to osteosclerotic metaphysial dysplasia. The molecular mechanism by which Lrrk1 regulates osteoclast function is unknown. Read More

    Lysosomal Ca(2+) Signaling is Essential for Osteoclastogenesis and Bone Remodeling.
    J Bone Miner Res 2017 Feb 26;32(2):385-396. Epub 2016 Sep 26.
    Department of Oral Physiology, and Institute of Biomaterial-Implant, College of Dentistry, Wonkwang University, Iksan, Republic of Korea.
    Lysosomal Ca(2+) emerges as a critical component of receptor-evoked Ca(2+) signaling and plays a crucial role in many lysosomal and physiological functions. Lysosomal Ca(2+) release is mediated by the transient receptor potential (TRP) family member TRPML1, mutations that cause the lysosomal storage disease mucolipidosis type 4. Lysosomes play a key role in osteoclast function. Read More

    A Novel ANO5 Mutation Causing Gnathodiaphyseal Dysplasia With High Bone Turnover Osteosclerosis.
    J Bone Miner Res 2017 Feb 9;32(2):277-284. Epub 2016 Sep 9.
    Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
    Gnathodiaphyseal dysplasia (GDD) is a rare skeletal syndrome that involves an osteopetrosis-like sclerosis of the long bones and fibrous dysplasia-like cemento-osseous lesions of the jawbone. Although the genetic analysis of the respective patients has revealed mutations in the ANO5 gene as an underlying cause, there is still no established consensus regarding the bone status of GDD patients. We report a new case of GDD in a 13-year-old boy with recurrent diaphyseal fractures of the femur, in whom we identified a novel de novo missense mutation in the ANO5 gene, causing a p. Read More

    Regulation and Function of Lentiviral Vector-Mediated TCIRG1 Expression in Osteoclasts from Patients with Infantile Malignant Osteopetrosis: Implications for Gene Therapy.
    Calcif Tissue Int 2016 Dec 19;99(6):638-648. Epub 2016 Aug 19.
    Nordic Bioscience, Herlev, Denmark.
    Infantile malignant osteopetrosis (IMO) is a rare, recessive disorder characterized by increased bone mass caused by dysfunctional osteoclasts. The disease is most often caused by mutations in the TCIRG1 gene encoding a subunit of the V-ATPase involved in the osteoclasts capacity to resorb bone. We previously showed that osteoclast function can be restored by lentiviral vector-mediated expression of TCIRG1, but the exact threshold for restoration of resorption as well as the cellular response to vector-mediated TCIRG1 expression is unknown. Read More

    Autosomal dominant osteopetrosis associated with renal tubular acidosis is due to a CLCN7 mutation.
    Am J Med Genet A 2016 Nov 19;170(11):2988-2992. Epub 2016 Aug 19.
    Academic Endocrine Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, University of Oxford, Oxford, United Kingdom.
    The aim of this study was to identify the causative mutation in a family with an unusual presentation of autosomal dominant osteopetrosis (OPT), proximal renal tubular acidosis (RTA), renal stones, epilepsy, and blindness, a combination of features not previously reported. We undertook exome sequencing of one affected and one unaffected family member, followed by targeted analysis of known candidate genes to identify the causative mutation. This identified a missense mutation (c. Read More

    Production of Osteoclasts for Studying Protein Tyrosine Phosphatase Signaling.
    Methods Mol Biol 2016 ;1447:283-300
    Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, 76100, Israel.
    Osteoclasts, specialized cells that degrade bone, are key components of the cellular system that regulates and maintains bone homeostasis. Aberrant function of osteoclasts can lead to pathological loss or gain of bone mass, such as in osteopetrosis, osteoporosis, and several types of cancer that metastasize to bone. Phosphorylation of osteoclast proteins on tyrosine residues is critical for formation of osteoclasts and for their proper function and responses to physiological signals. Read More

    Outcomes after Unrelated Umbilical Cord Blood Transplantation for Children with Osteopetrosis.
    Biol Blood Marrow Transplant 2016 Nov 25;22(11):1997-2002. Epub 2016 Jul 25.
    Eurocord, Hopital Saint Louis, Paris, France; Centre Scientifique de Monaco, Principality of Monaco; Churchill Hospital, University of Oxford, NHS Blood and Transplant (NHSBT), Oxford, United Kingdom.
    Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for most children with osteopetrosis (OP). Timing of HSCT is critical; therefore, umbilical cord blood transplantation (UCBT) is an attractive option. We analyzed outcomes after UCBT in 51 OP children. Read More

    Synonymous Mutations Add a Layer of Complexity in the Diagnosis of Human Osteopetrosis.
    J Bone Miner Res 2017 Jan 7;32(1):99-105. Epub 2016 Sep 7.
    Humanitas Clinical and Research Institute, Rozzano, Italy.
    Autosomal recessive osteopetroses (AROs) are rare, genetically heterogeneous skeletal diseases with increased bone density that are often lethal if left untreated. A precise molecular classification is relevant for the patient's management, because in some subgroups hematopoietic stem cell transplantation (HSCT), which is the only curative therapy, is contraindicated. In two unrelated ARO patients, the molecular analysis revealed the presence of a synonymous variant in known ARO genes, namely in the TCIRG1 gene in one patient and in the CLCN7 in the other patient, predicted to impact on the splicing process. Read More

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