Which are the causes of Limb-girdle muscular dystrophy?

Limb-girdle muscular dystrophy (LGMD) is a group of genetic disorders that primarily affect the muscles around the hips and shoulders. It is characterized by progressive muscle weakness and wasting, leading to difficulties in walking, climbing stairs, and performing everyday tasks. LGMD is a heterogeneous condition, meaning that it can be caused by various genetic mutations, each resulting in a slightly different form of the disease. Let's explore some of the known causes of Limb-girdle muscular dystrophy:

1. Genetic Mutations

The primary cause of LGMD is genetic mutations that affect the production or function of proteins involved in maintaining the structure and function of muscle cells. These mutations can be inherited in an autosomal dominant or autosomal recessive manner, depending on the specific gene involved.

Autosomal Dominant LGMD: In autosomal dominant LGMD, a single copy of the mutated gene is sufficient to cause the disease. Some of the genes associated with this form of LGMD include:

• LMNA: Mutations in the LMNA gene can lead to LGMD type 1B. This gene provides instructions for producing lamin A/C proteins, which are essential for maintaining the structure of the nucleus in muscle cells.


• DYSF: Mutations in the DYSF gene can cause LGMD type 2B. This gene encodes the dysferlin protein, which plays a crucial role in repairing muscle cell membranes.

Autosomal Recessive LGMD: Autosomal recessive LGMD requires two copies of the mutated gene, one from each parent, to manifest the disease. Some of the genes associated with this form of LGMD include:

• SARCOGLYCAN: Mutations in the SGCA gene can lead to LGMD type 2C. This gene provides instructions for producing the protein sarcoglycan, which is essential for maintaining the integrity of muscle cell membranes.


• CAVEOLIN3: Mutations in the CAV3 gene can cause LGMD type 1C. This gene encodes the caveolin-3 protein, which is involved in the formation of caveolae, small invaginations in the cell membrane that play a role in various cellular processes.

2. Protein Dysfunction

In LGMD, the genetic mutations often result in the production of abnormal or non-functional proteins. These proteins may disrupt the normal functioning of muscle cells, leading to muscle weakness and degeneration over time. The specific mechanisms by which these dysfunctional proteins contribute to the disease are still being studied.

3. Muscle Fiber Degeneration

LGMD is characterized by the progressive degeneration and loss of muscle fibers. The exact reasons behind this degeneration are not fully understood, but it is believed to be a consequence of the genetic mutations and protein dysfunction. The loss of muscle fibers leads to muscle weakness and atrophy, contributing to the symptoms of LGMD.

4. Inflammation and Immune Response

In some forms of LGMD, such as LGMD type 2B, inflammation and immune responses play a role in the disease progression. The dysferlin protein, which is mutated in LGMD type 2B, is involved in repairing muscle cell membranes. When dysferlin is dysfunctional, it can trigger an immune response and inflammation, further damaging the muscle fibers.

5. Other Factors

While genetic mutations are the primary cause of LGMD, other factors may influence the severity and progression of the disease. These factors include environmental factors, individual variations in gene expression, and potential interactions with other genes or proteins.

In conclusion, Limb-girdle muscular dystrophy is a group of genetic disorders primarily caused by mutations in genes involved in muscle structure and function. These mutations lead to protein dysfunction, muscle fiber degeneration, and in some cases, inflammation and immune responses. Understanding the underlying causes of LGMD is crucial for developing targeted therapies and interventions to manage the disease.

by Diseasemaps