The Diagnosis of Muscular Dystrophy

Chapter 2

Abstract

1. Introduction

9

and Elena Ionica

Clinical and Molecular Diagnosis

Muscular dystrophies are a diverse group of inherited muscle disorders with a wide range of clinical manifestations from a severe form with early onset and early death to adult forms with later onset and minimal clinical manifestation that do not affect life-span. Overlapping clinical symptoms and the multitude of genes that need to be analyzed for an accurate characterization make the diagnosis hard. In next-generation sequencing era, a lot of used assay in molecular diagnostics must be taken into consideration for muscular dystrophy diagnosis. However, for more accurate diagnosis, muscle protein expressions analysis may have prognostic value. In this chapter, we present the most important clinical and laboratory findings in the most common forms of muscular

dystrophies and molecular diagnostic approaches for a more accurate diagnosis.

Keywords: muscular dystrophy, multiplex Western blot, immunofluorescence, MLPA, hrMCA, dystrophin, calpain 3, DMD gene, CAPN3, genetic diagnosis

Muscular dystrophies (MD) are an inherited group of genetic disorders clinically characterized by progressive muscular weakness and wasting [1] and reduced skeletal muscle mass until their destruction due to a primary defect in the muscle cell. To date, there are known more than 30 different forms of MD with specific signs, symptoms, and genetic basis but sharing common histological features like variation in fiber shape and size and the presence of degeneration and regenerating fibers and connective tissue proliferation [2]. The diseases are distinguished from one another by the age of onset, muscles affected, as well as rate of disease progression [3]. While for some forms of MD, the initial symptoms manifested begin with childhood and have a rapid progression of muscle weakness causing the death of the patients around the age of 20 years, the other forms debut later in adulthood [4, 5] and have a slow rate of progression and an almost normal lifetime [6, 7]. Also, heart disease and mental retardation accompany some types of MD [8, 9], suggesting a different pathogenesis of the disease. It also found that there are subtypes of MD that share similar clinical manifestations and

However, the progress made in the past 33 years, since the first protein involved in a type of muscular dystrophy was discovered, leads to identify a large number of

For a rapid and an accurate diagnosis improvement in analysis, methods have become a necessity. The combination of clinical signs with muscle histopathology

different genetic defects with similar clinical manifestation [10, 11].

the genes as well as novel proteins involved in these muscle disorders [12].

Gisela Gaina, Magdalena Budisteanu, Emilia Manole

in Muscular Dystrophies
