Second Gene for Deafness

Scientists have found a second gene that, when mutated, can cause hearing loss but leave a person otherwise normal. The findings, reported in this month's issue of Nature Genetics, may help researchers figure out on a molecular level what goes wrong in deafness and eventually design a therapy, although any such possibility is far in the future.

Deafness has long been known to run in families, and while genes for about 60 syndromes that have deafness as one of multiple symptoms have been mapped, only last month did scientists locate the first of the estimated 100 genes that can cause hearing loss alone. Indeed, this second gene--the human equivalent of a mouse gene called shaker-1--already had a rap sheet for causing sensory problems. Two years ago, a French group found that mutations in the human version are associated with Usher syndrome type 1B, a condition that accounts for 4% to 10% of all cases of inherited deafness, but is associated with blindness as well. The French team and a British group that discovered the mouse gene both decided to see if the mutation--which hampers the production of a protein called myosin VIIA--might, as in the mice, explain inherited deafness without other sensory loss.

Teasing out the effect of single genes in deafness is difficult. A key challenge is that, at least in developed countries, deaf people tend to marry each other, thus mingling many genes for impaired hearing. To avoid that muddle, Steve Brown and Xue-Zhong Liu, molecular biologists at the Medical Research Council's Mouse Genome Center in Harwell, England, sought families in remote areas of the world, where the families' deafness is more likely to be caused by a single mutated gene. After examining eight such families from the Sichuan province of southeastern China, the duo discovered that in two of the families, the parents (who could hear) had one mutated copy of the gene for myosin VIIA. But all of the deaf children carried mutations on both copies of the gene.

The findings are backed up by a companion paper. Christine Petit, a molecular biologist at the Pasteur Institute in Paris, found that all 22 deaf individuals in a large family in southern Tunisia carry double copies of the myosin mutation. But family members who could hear had just one copy, and 100 unrelated people in the same region lacked the mutation altogether.

David Hughes, a molecular biologist at Nottingham University in England, says the finding "raises a new puzzle": Why does the same mutation leave some of its victims deaf, while those with Usher syndrome are struck deaf and blind? Petit speculates that those who are just deaf may somehow scrape together enough myosin VIIA--thought to help form the sound-detecting hairs in the inner ear--and devote it instead to the eye's rods and cones that detect light, where its role is critical, but unknown. And Brown notes that still-unidentified genes may moderate the effect of the mutation and spare the vision of most of the deaf.