Gene Discovery in Congenital Myopathy

  • Laura L. Smith
  • Vandana A. Gupta
  • Alan H. BeggsEmail author
Part of the Stem Cell Biology and Regenerative Medicine book series (STEMCELL)


The congenital myopathies (CMs) are a heterogeneous group of inherited neuromuscular disorders that manifest as skeletal muscle weakness at birth or early in life and are defined by the predominant morphological features observed on biopsy. However, accurate molecular diagnoses are frequently confounded due to the substantial clinical and histological overlap between different forms of CM and have been limited by traditional sequencing technologies. Today, scientific investigators and clinicians are strongly focused on understanding both the mechanistic basis of these devastating disorders and on gene discovery. The identification of new causative genes will have considerable impact on the approximately 30–40 % of CM cases where the genetic cause remains unknown, on disease management, and on the development of effective gene-specific therapies. This chapter will discuss the most common forms of CM and detail the methods of gene discovery that have shaped this field from past and present.


Congenital myopathy Nemaline myopathy Core myopathy Centronuclear myopathy Congenital fiber-type disproportion Disease gene discovery Animal models Skeletal muscle Sarcomere Triad 



Autosomal dominant


Autosomal recessive


Base pairs


Central core disease


Congenital fiber-type disproportion


Congenital myopathy


Centronuclear myopathy


Cytochrome c oxidase


Electron microscopy




Fiber size disproportion


Hematoxylin and eosin








Multiminicore disease


Magnetic resonance imaging


Nicotinamide adenine dinucleotide–tetrazolium reductase


Next-generation sequencing


Nemaline myopathy




Whole body MRI


Whole exome sequencing


Whole genome sequencing


X-linked myotubular myopathy


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Laura L. Smith
    • 1
  • Vandana A. Gupta
    • 1
  • Alan H. Beggs
    • 1
    Email author
  1. 1.Division of Genetics and GenomicsThe Manton Center for Orphan Disease Research, Boston Children’s Hospital, Harvard Medical SchoolBostonUSA

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