Gene Discovery in Congenital Myopathy

Abstract

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.