Muscular Dystrophies

Muscular dystrophy is a group of inherited diseases which characterized by progressive weakness and loss of muscle mass. The cause of  muscular dystrophy are mutations in genes  that affect muscle integrity and function. In many cases there is an elevated serum CK concentration and a dystrophic appearance of muscle in biopsy.

There are many different  types of muscular dystrophy  and the classification is based on the clinical pattern of weakness, mode of inheritance, age of onset and molecular defect.

Dystrophinopathies: Duchenne and Becker muscular dystrophy (DMD/bmd)

Dystrophinopathies are X-linked disorders which include muscle wasting diseases such as Duchenne Muscular dystrophy((DMD; MIM# 310200), Becker muscular dystrophy (BMD; MIM# 300376)  and Dilated Cardiomyopathy (CMD3B; MIM#302045). All forms of the disease are accompanied with elevated levels of CK including manifesting carriers which present approximately 18% of disease carries. The incidence of the various forms of dystrophinopathy is estimated to 1:12000 with most prominent the DMD phenotype.

DMD gene (Xp21.2, OMIM # 300377) is considered as largest protein-coding one with total genomic region 22MB, which encodes the muscle protein, dystrophin (kDa). It includes 79 exons and very large introns as intron 17 and intron and haw internal promoters with tissue-specific function intron 1 191.081 intron.

Tradionanally the routine analysis starts with deletion/duplication searching mainly via MLPA analysis followed by sequencing of the gene coding region.

Limb Girdle Muscular Dystrophy

Limb-girdle muscular dystrophy or (LGMD) is a group of rare  muscular dystrophies with clinical and genetic heterogeneity They present It is characterised by progressive muscle wasting which affects predominantly hip and shoulder muscles. LGMD has an autosomal pattern of inheritance (dominant or recessive) and currently has no known cure or treatment.

There are more 30 different types of the disease with most common LGMDR1 (# 253600) .

The diagnosis of disease,  is established by identification of  pathogenic variants in CAPN3 gene in chromosomal region 15q15.1  (encoding proteolytic enzyme calpain-3 by sequencing or MLPA analysis).

Oculopharengeal Muscular Dystrophy (OPMD)

OPMD is a rare genetic myopathy with onset during adulthood most often between 40 and 60 years of age. The patients develop weakness initially  in eye muscles (ptosis) and  throat muscles and later in their limbs. The mode of inheritance is autosomal dominant

The diagnosis of the disease is established by identification of a gene triplet repeat expansion in PABPN1 gene ( 14q11.2) using TriplePrime-PCR analysis.