1. Duchenne Muscular Dystrophy and Becker Muscular Dystrophy


Dystrophin is one of the largest known genes, consisting of almost 0.1% of the human genome (2,500 Kbp). The product of the DMD gene in normal muscle, dystrophin, is a 427 kDa protein. Dystrophin is part of a large protein complex, the dystrophin-associated glycoprotein complex (DAGC) which is a multicomponent complex which includes the dystroglycans, the sarcoglycans, the syntrophins, and sarcospan. Dystrophin interacts with several members of the complex, which forms a mechanical as well as signaling link from the extracellular matrix to the cytoskeleton. Mutations in dystrophin result in membrane damage, allowing massive infiltration of immune cells, chronic inflammation, necrosis, and severe muscle degeneration. The frequency of intragenic deletions varies in different populations across the globe. The American studies report mutant alleles with gene deletions in 55-70% of all DMD/BMD cases. In European and Asian studies much lower frequency of deletions were observed.


BMD is similar to DMD but less severe. It is estimated to occur at one tenth the frequency of DMD. The disorder is inherited with an X-linked recessive inheritance pattern. It often results from in-frame mutations of the dystrophin gene that allow production of an altered but partially functional protein.


2. Limb Girdle Muscular Dystrophy


Table1: Autosomal Dominant


Table 2: Autosomal Recessive




3. Facioscapulohumeral Muscular Dystrophy (FSHD)


FSHD is due to deletions of integral copies of D4Z4 units at the 4q35 locus. These arrays are in subtelomeric regions of 4q and 10q and have 1-100 units. In most patients with FSHD, the D4Z4 repeat is contracted to an array of 1-10 units, and, at least one unit of D4Z4 is required to develop FSHD. Loss of a critical number of D4Z4 repeats compromises the structure of an FSHD gene located within the repeats. Each D4Z4 repeat contains a single open reading frame encoding a putative double homeobox gene, designated DUX4. Unambiguous clinical diagnosis of FSHD depends on determining the array length at 4q35.


4. Oculopharyngeal muscular dystrophy


OPMD is genetically characterized by a mutation in the polyadenylate binding protein nuclear 1 (PABPN1) gene. This condition was initially genetically mapped to chromosome 14q11.2-q13 in French Canadian families in whom prevalence of the disease is the highest reported anywhere in the world. The first exon of the PABPN1 gene normally contains a (GCG)6 trinucleotide repeat, which is abnormally expanded to 8–13 triplets in patients with OPMD. The mode of inheritance is autosomal dominant in most families, but autosomal recessive cases have also been documented.


5. Emery Dreifuss Muscular Dystrophy


EDMD shows two forms of inheritance patterns, X-linked recessive and autosomal dominant EDMD (AD-EDMD) and autosomal recessive EDMD (AR-EDMD).

The gene responsible for the X-linked form is located on chromosome Xq28. Of the eight genes in this region which were highly expressed in brain and muscle, one in particular, STA was found in the affected individual.  The STA gene is 2100 bp in length, consists of six exons and encodes 762 bp mRNA. Its 34 KD protein product of 254 amino acids has been designated as 'emerin'.

The gene responsible for the autosomal dominant and recessive form is LMNA and located on chromosome 1q11-q23. This gene spans approximately 24 kb and is composed of 12 exons. Alternative splicing within exon 10 gives rise to two different mRNAs: a 1992 bp mRNA that codes for pre-lamin A and a 1716 bp mRNA that codes for lamin C. Consequently, two proteins are generated, lamin A (664 aa, 74 kDa) and lamin C (572 aa, 64 kDa).

Emerins and Lamins are members of the intermediate filament protein family and major components of the nuclear envelope.


6. Congenital Muscular Dystrophy


The congenital muscular dystrophies are inherited in an autosomal recessive manner with the exception of collagen VI-deficient CMD which may be inherited in an autosomal recessive or an autosomal dominant manner and LMNA-related CMD (L-CMD) which is inherited in an autosomal dominant manner with all cases to date caused by de novo mutation.

There are currently 12 genetically defined forms of CMD that fall into three groups on the basis of the classes of proteins that are affected. Several forms of CMD are caused by mutations in genes encoding structural proteins of the basement membrane or extracellular matrix of skeletal muscle fibers: collagen VI, laminin a2 and a7-integrin. Mutations in genes encoding putative or proven glycosyltransferase enzymes POMT1, POMT2, POMGnT1, fukutin, FKRP and LARGE involved in the glycosylation of dystroglycan result in a number of forms of CMD, often associated with neuronal migration defects. Mutations in the SEPN1 gene, which encodes an endoplasmic reticulum protein of unknown function, are associated with CMD with rigid-spine syndrome.



7. Myotonic Muscular Dystrophy


Two genes associated with myotonic dystrophy are DMPK gene causing myotonic dystrophy type 1, while type 2 results from mutations in the CNBP gene. Both types of myotonic dystrophy are inherited in an autosomal dominant pattern. The protein produced from the DMPK gene may play a role in communication within cells. It appears to be important for the correct functioning of cells in the heart, brain, and skeletal muscles. The protein produced from the CNBP gene is found primarily in the heart and in skeletal muscles, where it probably regulates the function of other genes.

Similar changes in the structure of the DMPK and CNBP genes cause the two forms of myotonic dystrophy. It is caused due to an unstable trinucleotide repeat expansion containing cytosine-thymidineguanosine (CTG) n, located in the 3’ untranslated region of chromosome 19q13.3. The CTG trinucleotide is repeated in the normal population from 5 to 36 times but has been found to be expanded up to 2000 times in myotonic dystrophy patients. This amplification is correlated to the severity of the disease.  The mutated gene produces an expanded version of messenger RNA. The abnormally long messenger RNA forms clumps inside the cell that interfere with the production of other proteins. These changes prevent muscle cells and cells in other tissues from functioning normally, which leads to the signs and symptoms of myotonic muscular dystrophy.


8. Distal Muscular Dystrophy


Distal muscular dystrophy is a heterogeneous type of muscular dystrophy. The inheritance pattern and genes involved for different types are enumerated below.




Jeegar Mota

Cell # 9821151851

Chandu Kant

Cell # 9223363874

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