Berlin — Researchers at the Max Planck Institute for Molecular Genetics and colleagues from Nijmegen University have discovered that mutations of the SMPX (small muscle protein) gene, located on the X chromosome, is a previously unknown genetic cause of progressive hearing impairment.

Until now, the gene had been known to be active in the skeletal muscle and heart, but it was not known to play a role in hearing. The discovery will make it easier to diagnose progressive hearing impairment and may also provide a starting point for the development of new treatment methods.

Hereditary hearing loss has many causes: researchers have already identified over 50 genes with different functions that could be considered as possible triggers of the disease. However, it is not the only cause of the condition that differs from case to case.

The pattern of inheritance is also highly variable. This wide range of possible causes makes it difficult to diagnose the cause of hearing loss and thus poses problems for doctors when counseling patients and their families.

“In our study, we succeeded in demonstrating for the first time that SMPX is very active in the inner ear,” says Vera Kalscheuer, a scientist at the Max Planck Institute for Molecular Genetics.

The researchers were also surprised the mutation only affects the hearing, while the function of the muscles and heart is not impaired.

The disease-causing mutation involves the substitution of a single base in the genetic material. The mutation in the genetic code causes a premature stop codon. The missing information results in either the premature degradation of the mutated gene transcript or the truncation of the protein, which is unable to function correctly as a result. Contrary to most X-chromosome disorders, women are also affected by the disease, though usually less severely.

The precise role played by the protein in the hearing process, the blueprint of which is encoded in the SMPX gene, is presently unknown. The researchers suspect that it is important for the development of the hair cell projections of the cochlea. These fine structures react to sound waves and are responsible for transforming sounds into electrical potential and transmitting them to the auditory center in the brain. Accordingly, the malfunctioning of these cells, which are known as stereocilia, could be responsible for the hearing impairment.

“Our discovery makes hearing impairment easier to diagnose,” Kalscheuer says. “Up to now, we could only speculate about the function of the SMPX protein.”

The next step is to identify the precise role that the protein plays in the hearing process by carrying out functional tests. Kalscheuer added, “When we know the precise mechanism at work here, we can carry out further research and possibly develop new treatment options.”

SOURCE: Max Planck Institute for Molecular Genetics