The MYO7A gene holds the code for producing a protein named myosin VIIA. This protein is produced in specialized cells within the inner ear and the eye, where it performs functions necessary for normal hearing, balance, and vision. When the MYO7A gene has a harmful change, or mutation, the myosin VIIA protein cannot function correctly, leading to a range of related health conditions.
The Role of the MYO7A Protein
The myosin VIIA protein is a member of a family of proteins known as unconventional myosins. These proteins act as microscopic motors within cells, moving along tracks made of another protein called actin to transport cellular cargo. Myosin VIIA also serves as a structural anchor, ensuring that specific cellular components are correctly positioned.
In the inner ear, myosin VIIA is active in the sensory cells responsible for hearing and balance. These cells have tiny, hair-like projections called stereocilia that bend in response to sound waves and head movements. Myosin VIIA is required for the proper development and structural integrity of these stereocilia bundles, helping to maintain their organized structure to convert mechanical stimuli into nerve signals. Without functional myosin VIIA, these delicate structures become disorganized, impairing both hearing and balance.
In the retina, the light-sensitive tissue at the back of the eye, myosin VIIA is found in a layer of cells called the retinal pigment epithelium (RPE). The RPE supports and nourishes the light-detecting photoreceptor cells. Within the RPE, the protein helps transport melanosomes—sacs containing pigment for normal vision—and moves other molecules important for the retina’s function.
Associated Genetic Conditions
Changes in the MYO7A gene can lead to several distinct genetic conditions, with the diagnosis often depending on the mutation’s severity. The most common condition is Usher syndrome type 1B (USH1B), the most severe form of the disorder, which combines hearing loss, vision loss, and balance problems.
The same gene can also cause hearing loss without the associated vision problems, referred to as nonsyndromic deafness. These conditions manifest in two primary forms. DFNB2 involves profound hearing loss from a young age, while the rarer DFNA11 causes progressive hearing loss starting later in childhood.
Symptoms and Progression
The clinical journey for individuals with MYO7A-related conditions varies depending on the specific disorder. Those with Usher syndrome type 1B are born with profound deafness in both ears. They also experience severe balance problems (vestibular dysfunction) originating from inner ear abnormalities, which often causes delays in milestones like sitting and walking.
The vision loss associated with USH1B is caused by retinitis pigmentosa (RP), with symptoms emerging during childhood or adolescence. RP begins with difficulty seeing in dim light (night blindness), followed by a slow, progressive loss of peripheral vision. Over many years, this can lead to “tunnel vision” and, in some cases, legal blindness.
In contrast, the symptoms for DFNB2 and DFNA11 are confined to hearing. Individuals with DFNB2 experience profound hearing loss from birth or adolescence, and some may have balance issues. DFNA11 involves a moderate to severe hearing loss that begins after a child has learned to talk and worsens over time.
Inheritance and Diagnosis
Usher syndrome type 1B and the nonsyndromic deafness condition DFNB2 are inherited in an autosomal recessive pattern. This means for an individual to be affected, they must inherit two mutated copies of the MYO7A gene—one from each parent. The parents, who each carry only one mutated copy, are known as carriers and do not show symptoms themselves.
A different pattern applies to the rarer DFNA11 form of deafness, which is inherited in an autosomal dominant pattern. Inheriting just one mutated copy of the MYO7A gene from one parent is enough to cause the disorder, and affected individuals have a 50% chance of passing it to each child.
A definitive diagnosis for these conditions is achieved through genetic testing, which analyzes an individual’s DNA for mutations in the MYO7A gene. Identifying the specific genetic change confirms the diagnosis, helps predict the condition’s course, and provides clear information for family planning.
Management and Future Research
Currently, there is no cure for conditions caused by MYO7A mutations, so management focuses on addressing symptoms. For the profound hearing loss in Usher syndrome type 1B and DFNB2, cochlear implants can be surgically placed to provide a sense of sound and are most effective when implanted early in life. Management for the progressive vision loss of Usher syndrome includes orientation and mobility training, the use of low-vision aids, and wearing UV-blocking sunglasses.
Gene therapy is a primary focus of research for future treatments. The goal is to deliver a correct copy of the MYO7A gene to the cells in the retina to halt the progression of vision loss. Researchers are developing methods using harmless viruses, known as viral vectors, to carry the functional gene into retinal cells.
Because the MYO7A gene is too large for a single standard vector, scientists are pioneering “dual vector” systems to deliver the gene in two pieces. This technique is now being tested in clinical trials.