Israeli researcher identifies gene that causes deafness

NEW YORK — An Israeli geneticist has discovered a defective gene that causes progressive hearing loss.

Karen Avraham of Tel Aviv University led an international team of researchers who found that the autosomal dominant gene, DFNA15, caused moderate to severe deafness by age 40 in one large Israeli family.

"This is really the beginning of understanding the molecular bearings of hearing loss," said Avraham.

The finding is also a first step toward using genetic manipulation to correct hearing loss.

The DFNA15 gene regulates the function of many other genes, so the ability to isolate and correct that gene would affect the function of other genes that control hearing.

The findings are documented in the March 20 issue of the journal Science.

Avraham studied an Israeli family, tracing the gene mutation back five generations to an ancestor born in 1843 in Libya. Branches of the family now live in Israel, the United States and Belgium.

Of 80 living members, 50 percent inherited the defective gene. The onset of hearing loss begins at about age 18, and males and females are equally likely to become deaf.

The gene is not thought to occur more frequently among Jews, but the study required the participation of a large family affected by deafness.

She said deaf people often prefer to marry others who are deaf, even though they may have suffered hearing loss for different reasons.

"A family is where you see the disease segregating," Avraham said in a telephone interview from Italy. "In Israel, families tend to stay close together."

The gene was located near another gene for inherited deafness identified a few months ago by researchers at the University of Washington. Of some 100 genes scientists believe exist for deafness, the chromosomal location of 31 of these has been mapped.

Research from mice was utilized to isolate the gene. As a postdoctoral fellow at the National Cancer Institute in 1995, Avraham cloned a gene, Myosin VI, which causes deafness in mice.

Studying that gene led the geneticists to another gene known to be crucial for the normal development of hearing in mice. When the human form of the same gene, known as POU4F3, was sequenced using DNA from hearing-impaired individuals in the Israeli family, a mutation was found in a critical part of the gene.

Deaf members of the Israeli family carry two forms of the defective gene, one normal and one mutant. The normal gene appears to be dominant until around the age of 18, when the progressive hearing loss becomes noticeable.

At that point, researchers believe the mutant gene takes over, preventing the normal gene from functioning properly. By age 40, affected individuals cannot hear without a hearing aid.

"The next step is to see if there will be mutations of this gene in other populations," said Avraham.