A 2-hour exposure to loud noise, similar to that of loud rock bands, is enough to seriously damage cilia bundles on the hair cells of a cat's inner ear. Normal mammalian hair cell bundles have two or three parallel rows of cilia, one taller than the next. The tall cilia are most vulnerable to noise.
After exposure to loud noise, all the tall cilia on the right of this picture have disappeared or fused together and fallen over.
Photo: Michael J. Mulroy and M. Charles Leberman, Massachusetts Eye and Ear Infirmary
Being able to hear speech is so taken for granted"Is it possible for a hearing person to comprehend the enormity of its absence in someone else?" asks Hannah Merker in her poignant book Listening. "The silence around me is invisible...."
Most of the 28 million deaf or hearing-impaired people in the United States were born with normal hearing, as was Merker, who became deaf after a skiing accident in her twenties. Their deafness generally results from overexposure to loud noise, disease, or old age. But genetic factors are also an important cause of hearing loss, especially in children.
It is estimated that 1 in every 1,000 newborns is profoundly deaf, while nearly 1 in 20 has a significant hearing impairment. In more than half of these cases, the cause is genetic.
Deafness is associated with over 100 different genetic disorders, however. Since there is often no obvious difference between deafness that is caused by different genes, finding the genes involved has proved quite difficult. Scientists could not simply group together families with the same disorder and then try to localize the guilty gene, the usual method. Instead, they had to seek large families whose members were likely to have the same genetic defect. The number of people available for such studies was relatively small.
One "deafness" gene was discovered in 1995 by following a trail that started nearly three quarters of a century ago, when researchers noticed a very peculiar mutant mouse. The mouse kept running around in circles, tossing its head and staggering as it moved. It clearly had a problem with its balance. It was also profoundly deaf. The researchers named it "shaker" because of its distinctive motion and started a colony of pure-bred offspring that has been maintained ever since. They believed it would be of use someday.
Several years ago, a group of scientists who were studying deaf mice at the MRC Institute of Hearing Research in Nottingham, England, decided to focus on a subgroup of these mutants, "shaker-1". They generated 1,066 mice of this type, analyzed their DNA, and eventually isolated a gene on mouse chromosome 7 for a protein called myosin VIIA. This was very fortunate, since the region of mouse chromosome 7 in which the gene was located is the equivalent of a stretch of human chromosome 11 that was linked to Usher syndrome type 1B, a genetic deafness. The coincidence gave scientists a hint that the two disorders might be related.
Children with Usher syndrome are born with "absolutely profound deafness," says David Corey. In addition, their vestibular system is gone, so they have no sense of balance. Around 10 years of age they start to go blind. "By the age of 30, they can't hear, can't see, and have trouble walkingit's a terrible disease," Corey says. About 1 in 70 people are carriers of this defect. If two carriers marry, their children have one chance in four of inheriting the disease.
Realizing that the myosin gene they isolated in mice might also be the cause of Usher syndrome, the British scientists asked researchers who worked with deaf families in France and Nebraska to search for myosin mutations in their patients' DNA. Both research groups soon found many examples of such mutations.
Since then, David Corey's group and others have sequenced the myosin VIIA gene and have found that in the ear this myosin is made only by hair cells. He thinks the protein may act at the cross-links between adjacent cilia in each hair-cell bundle.
More recently, European researchers have found other mutations in the myosin VIIA gene that lead to profound deafness alonenot to blindness. Meanwhile Corey and others are looking for different proteins that bind to myosin VIIA, in the hope of discovering genes for other types of deafness and, eventually, new kinds of treatment.