MYO7A

Researchers have identified several MYO7A gene mutations that can cause nonsyndromic hearing loss, which is loss of hearing that is not associated with other signs and symptoms. Mutations in this gene are thought to cause two forms of nonsyndromic hearing loss: DFNA11 and DFNB2.

DFNA11 is inherited in an autosomal dominant pattern, which means only one mutated copy of the MYO7A gene in each cell is sufficient to cause the condition. This form of hearing loss begins in childhood, after a child learns to speak (postlingual), and becomes more severe over time.

Most of the mutations that cause DFNA11 alter a single protein building block (amino acid) in myosin VIIA, resulting in an abnormal protein that does not work properly. Other genetic changes delete a small amount of DNA from critical regions of the MYO7A gene, which probably changes the structure of the protein. Researchers suspect that the altered protein causes hearing loss by disrupting the growth and organization of stereocilia in the inner ear.

DFNB2 is inherited in an autosomal recessive pattern, which means both copies of the MYO7A gene are mutated in each cell. The hearing loss can be postlingual or begin before a child learns to speak (prelingual). Some researchers have suggested that individuals with DFNB2 may actually have Usher syndrome (described below), because some individuals who were thought to have nonsyndromic hearing loss developed retinitis pigmentosa (a vision disorder characteristic of Usher syndrome) later in life. However, other individuals diagnosed with DFNB2 never develop retinitis pigmentosa, and recent studies indicate that DFNB2 and Usher syndrome probably result from different mutations in the MYO7A gene.

The mutations that cause DFNB2 alter the structure and function of myosin VIIA, but they probably do not eliminate the protein's function completely. Recent studies found that the protein likely retains enough function in the retina to allow for normal vision, but not enough function in the inner ear to permit normal hearing.

More than 200 mutations in the MYO7A gene have been identified in people with Usher syndrome type I, which is characterized by a combination of hearing loss, vision loss, and problems with balance and coordination. Specifically, MYO7A gene mutations cause a form of the disorder known as Usher syndrome type IB (USH1B), which accounts for more than half of all cases of Usher syndrome type I.

Many of these genetic changes alter a single protein building block (amino acid) in critical regions of the myosin VIIA protein. Other mutations introduce a premature stop signal in the instructions for making myosin VIIA. Still other mutations insert or delete small amounts of DNA in the MYO7A gene. All of these changes lead to the production of a nonfunctional version of myosin VIIA or prevent the production of any of this protein. A lack of myosin VIIA in the inner ear disrupts the normal development and function of stereocilia, which leads to hearing loss and difficulty with balance and coordination. A lack of myosin VIIA in the retina causes retinitis pigmentosa, a condition in which light-sensing cells of the retina gradually deteriorate, resulting in progressive vision loss.

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