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pp 1-27 | Cite as

Genetics of Skeletal Disorders

  • Fadil M. Hannan
  • Paul J. Newey
  • Michael P. Whyte
  • Rajesh V. ThakkerEmail author
Chapter
Part of the Handbook of Experimental Pharmacology book series

Abstract

Bone and mineral diseases encompass a variety of conditions that involve altered skeletal homeostasis and are frequently associated with changes in circulating calcium, phosphate, or vitamin D metabolites. These disorders often have a genetic etiology and comprise monogenic disorders caused by a single-gene mutation, which may be germline or somatic, or an oligogenic or polygenic condition involving multiple genetic variants. Single-gene mutations causing Mendelian diseases are usually highly penetrant, whereas the gene variants contributing to oligogenic or polygenic disorders are each associated with smaller effects with additional contributions from environmental factors. The detection of monogenic disorders is clinically important and facilitates timely assessment and management of the patient and their affected relatives. The diagnosis of monogenic metabolic bone disorders requires detailed clinical assessment of the wide variety of symptoms and signs associated with these diseases. Thus, clinicians should undertake a systematic approach commencing with careful history taking and physical examination, followed by appropriate laboratory and skeletal imaging investigations. Finally, clinicians should be familiar with the range of molecular genetic tests available to ensure their appropriate use and interpretation. These considerations are reviewed in this chapter.

Keywords

Bone Genetic Next-generation sequencing Osteoporosis Variant 

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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Fadil M. Hannan
    • 1
  • Paul J. Newey
    • 2
  • Michael P. Whyte
    • 3
    • 4
  • Rajesh V. Thakker
    • 5
    Email author
  1. 1.Nuffield Department of Women’s and Reproductive HealthUniversity of OxfordOxfordUK
  2. 2.Division of Molecular and Clinical Medicine, Ninewells Hospital and Medical SchoolUniversity of DundeeDundeeUK
  3. 3.Center for Metabolic Bone Disease and Molecular ResearchShriners Hospitals for Children – St. LouisSt. LouisUSA
  4. 4.Division of Bone and Mineral Diseases, Department of Internal MedicineWashington University School of Medicine at Barnes-Jewish HospitalSt. LouisUSA
  5. 5.Academic Endocrine Unit, Radcliffe Department of MedicineUniversity of OxfordOxfordUK

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