New Class of Deafness Gene Identified

Scientists have discovered a new class of gene that is essential for hearing and balance, according to a new study reported in the August 1998 issue of the journal Nature Genetics. Mutations of a gene that codes for the protein Atp2b2, were identified in two types of the deafwaddler (dfw) mouse mutant. One mouse mutant, the dfw, is deaf and displays imbalance by waddling and bobbing its head while walking. The second mutant, the dfw^2J, is also deaf but unable to walk because of its severe balance problems.

"The gene codes for the protein Atp2b2, a plasma membrane calcium ATPase," said investigator Konrad Noben-Trauth, Acting Chief of the Section on Murine Genetics at the National Institute on Deafness and Other Communication Disorders (NIDCD). The function of this protein is to pump calcium from the inside to the outside of cells.

"The research team, which included Valerie Street, Ph.D., Bruce Tempel, Ph.D. and colleagues from the Virginia Merrill Bloedel Hearing Research Center and Department of Otolaryngology-Head and Neck Surgery, University of Washington School of Medicine, Seattle, Washington, found that in dfw a spelling error in the genetic code interferes with the function of the protein to pump calcium across the membrane. In the dfw^2J, two letters of the genetic code were found to be missing, leading to a shortened protein which probably has no function at all," he explained. The Atp2b2 protein is the predominant member of the Atp2b gene family that is expressed in auditory and vestibular hair cells, the primary receptor cells for hearing and balance.

Balance and hearing are controlled by sensory hair cells in the inner ear through a process called mechano-electrical transduction. Mechano-electrical transduction begins when mechanical sound waves that originate when a force causes an object to vibrate, enter the inner ear and set the inner ear fluid into motion. The hair cells, which reside on a membrane within the inner ear, move when the fluid moves the membrane they are resting on. The movement of these hair cells opens up channels that create electrical changes within the hair cell. It is at this time that more calcium enters the cell. This calcium needs to be removed before the cell can return to its resting position to allow the process to begin again. Atp2b2 appears to play a crucial role in the electrical signal transduction as well as the removal of the calcium from the hair cell. A similar process occurs within the vestibular/balance system when head movements or motion cause the inner ear hair cells of the balance system to move, creating electrical changes within those hair cells as well.

"The Atp2b2 gene was found on mouse chromosome 6 which corresponds to part of human chromosome 3 (3p25-26) where a gene, DFNB6, has already been identified as causing deafness in humans," explained Dr. Noben-Trauth. "Our research has excluded the ATP2B2 gene, the human counterpart of Atp2b2 gene, as the cause of this particular type of deafness, but further research should determine whether the ATP2B2 gene is involved in other similar types of deafness," he added.

"The discovery of this first plasma membrane calcium pump gene for hearing and balance is another giant leap toward improved understanding of the functions of the ear and has the potential of benefiting many individuals," commented NIDCD Director James F. Battey, Jr., M.D., Ph.D.

As the nation's focal point for research in human communication, the NIDCD conducts and supports biomedical and behavioral research and research training on normal mechanisms as well as diseases and disorders of hearing, balance, smell, taste, voice, speech and language that affect 46 million Americans.

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