ANO5

At least three ANO5 gene mutations have been identified in people with a bone disorder called gnathodiaphyseal dysplasia, which leads to fragile bones, jaw problems, and other skeletal abnormalities. The ANO5 gene mutations that cause gnathodiaphyseal dysplasia change single protein building blocks (amino acids) in the anoctamin-5 protein. It is unclear how these mutations lead to the signs and symptoms of gnathodiaphyseal dysplasia, or why they primarily affect bones while other ANO5 gene mutations cause muscle disorders. Researchers suggest that the mutations may affect the way cells process calcium, an important mineral in bone development and growth.

More than 40 mutations in the ANO5 gene have been identified in people with limb-girdle muscular dystrophy type 2L. Limb-girdle muscular dystrophy is a group of related disorders characterized by muscle weakness and wasting (atrophy), particularly in the shoulders, hips, thighs, and upper arms.

The ANO5 gene mutations identified in people with limb-girdle muscular dystrophy type 2L change single amino acids in the anoctamin-5 protein sequence, disrupt how genetic information is pieced together to make a blueprint for producing the protein, or result in a premature stop signal that leads to an abnormally short protein. One of the mutations adds an extra DNA building block (nucleotide) to the ANO5 gene (written as 191dupA) and is believed to be a relatively common cause of limb-girdle muscular dystrophy in people with northern European ancestry. This mutation alters the instructions used to make the anoctamin-5 protein, leading to a premature stop signal that would produce an abnormally short protein. Instead, a cellular error-catching mechanism called nonsense-mediated decay prevents the protein from being produced at all.

ANO5 gene mutations that eliminate or impair the role of the anoctamin-5 protein as a chloride channel likely lead to impaired muscle function, resulting in the signs and symptoms of limb-girdle muscular dystrophy.

At least 10 mutations in the ANO5 gene have been found to cause Miyoshi myopathy. When caused by mutations in this gene, the condition is also known as distal anoctaminopathy. Miyoshi myopathy is a muscle disorder that is characterized by progressive weakness and atrophy of muscles that are away from the center of the body (distal muscles), particularly those in the legs. The ANO5 gene mutations identified in people with Miyoshi myopathy change single amino acids in the anoctamin-5 protein or result in the production of an abnormally short protein that is quickly broken down.

These mutations result in the production of little or no anoctamin-5 protein. The effects of the loss of anoctamin-5 are unclear. While chloride is necessary for normal muscle function, it is unknown how a lack of this chloride channel causes the signs and symptoms of Miyoshi myopathy.

The 191dupA mutation that can cause limb-girdle muscular dystrophy (described above) is also a common cause of Miyoshi myopathy in individuals of northern European ancestry. It is not known why the 191dupA mutation can result in different patterns of signs and symptoms. Miyoshi myopathy caused by ANO5 gene mutations is likely a variation of limb-girdle muscular dystrophy because it is caused by mutations in the same gene, and in some cases even by the same mutation.