Genes of Silence: Scientists Track Down a Slew of Mutated Genes That Cause Deafness

Article excerpt

On the north shore of the island of Bali sits Bengkala, a 700-year-old village that has earned a measure of fame for its remarkably large number of deaf people--currently 48 of the nearly 2,200 inhabitants. These deaf residents have had a profound influence on Bengkala's culture.

"This is a very unusual community. The village has created a unique sign language, and most people in the village have some facility with it," says John T. Hinnant of Michigan State University in East Lansing, an anthropologist who has recently spent time documenting the village's culture on videotape.

Signed names have replaced spoken names. Villagers refer to Hinnant by making the sign for a videocamera or, he ruefully admits, the sign for a big nose.

Bengkala isn't fertile scientific ground just for anthropologists. Hinnant learned of the village from geneticists who are working to isolate the mutated gene responsible for the widespread hearing loss. So far, they've localized the gene to a small region of chromosome 17.

"We're quite close to having it," says Thomas B. Friedman of the National Institute on Deafness and Other Communication Disorders in Bethesda, Md.

Once found, the Bengkala gene will join the numerous other genes that investigators have recently tied to hearing loss. Last year was "quite dizzy with deafness genes," remarks Karen P. Steel of the Medical Research Council's Institute of Hearing Research in Nottingham, England.

These new genes are providing some of the first molecular insights into the workings of the auditory system and into the reasons why about 1 child in 1,000 is born deaf. Mutations in some of the genes produce hearing loss alone. In other cases, the gene mutations cause a range of other problems as well, such as blindness.

While the identification of these deafness genes may not help people born with profound, almost always permanent hearing loss, it may benefit the many whose deafness strikes later in life. "If you know at a biological level what's going wrong in the ear, you at least have a chance of intervening, preventing the hearing loss from getting any worse, or maybe even reversing it," says Steel.

Discerning the origins of deafness, genetic or otherwise, is no easy task indeed, physicians often cannot diagnose the flaw that eliminates a person's perception of sound.

A person's ability to hear depends on the spiral-shaped cochlea, a pea-size organ in the inner ear. In each cochlea, a mere 16,000 hair cells, each bearing a cap of bristles called stereocilia, detect noises. Sound-induced movement of the stereocilia stimulates the hair cells to generate electric impulses that convey auditory information to the brain. Physicians suspect that most cases of deafness stem from problems with the hair cells--but that's tough to confirm, since the cochlea is hidden within a bony labyrinth.

Resolving the genetics of deafness is no less challenging. Genetic flaws account for about half the incidence of congenital deafness, but researchers estimate that mutations in more than a hundred genes may trigger such hearing loss. This genetic diversity shows up in the striking fact that the majority of children born to two deaf parents can hear.

Scientists have been able to find many genes responsible for the syndromic forms of deafness, in which hearing loss is accompanied by other symptoms. In 1992, for example, investigators found the mutated gene behind Waardenburg's syndrome, a condition characterized by deafness, widely spaced eyes that are sometimes mismatched in color, and a white forelock (SN: 5/2/92, p. 296). Last year, several research groups examining people with deafness, frequent loss of consciousness, and a dangerous heart arrhythmicity attributed the syndrome to mutations in various genes that encode components of a protein complex that allows potassium ions to enter cells.

In contrast, investigators have struggled to find genes behind nonsyndromic deafness, which is the far more common type, accounting for the majority of congenital hearing loss. …