Oct. 21, 1999 Chapel Hill - A new study at the University of North Carolina at Chapel Hill is the first to establish that a mutation in a gene associated with about 20 percent of all cases of hereditary deafness found in Whites is also found in Blacks.
"There have been some reports in the scientific literature on Caucasians but only a small study on African-Americans, and they didn't find the mutation," said Dr. Elizabeth M. Rohlfs, clinical assistant professor of pathology and laboratory medicine at UNC-CH School of Medicine.
Rohlfs and her colleagues tested DNA samples of 500 Whites and 500 Blacks for the mutation known as 35-delete-G (35delG). Healthy carriers of the mutation carry only one copy, from either their mother or father. When each parent has a copy, one in four offspring risk inheriting a pair and is born deaf. These are the odds for inheriting a recessive genetic trait.
"We found a 2 percent carrier frequency of 35-delete-G in Caucasians and a 0.4% carrier frequency in African- Americans," Rohlfs said. In the North Carolina general population, this translates to a frequency of one in 10,000 for Whites and 1 in 250,000 for Blacks.
The findings will be reported Wednesday October 20 to the annual meeting of the American Society of Human Genetics in San Francisco. They provide important population-based statistics that will help form the basis for wider genetic screening for 35delG.
"This study suggests that 35-delete-G may account for a significant proportion of recessive deafness not linked to another genetic disorder in North Carolina," Rohlfs said.
The mutation, a deletion of a single nucleic acid, occurs in the gene responsible for connexin 26, a protein crucial to communication between cells, including cells within the inner ear.
The protein makes the infinitesimally small gap junctions in cell membranes that allow molecules to pass through to adjacent cells. In the inner ear, gap junctions play an important role in the physiology of hearing. Auditory signals emanating from hair cells deep within inner ear canals depend upon the flow of potassium. Gap junctions allow potassium to flow from hair cells to neighboring cells. As hair cells are the first to respond to sound vibrations, a connexin mutation that interferes with efficient potassium transport could result in a hearing loss.
UNC is a leader in the treatment of hearing loss in children. It is also a center for cochlear implant surgery. These devices help restore auditory input. But some youngsters do not benefit from them as much as others. So far no one has ever systematically looked at whether or not the underlying cause of deafness influences the efficacy of cochlear implant.
"We'd like to determine if there's some underlying cause of the hearing loss so we can predict who will do well with cochlear implants and who's not going to do well," said Dr. Carol G. Shores, chief resident in UNC's division of otolaryngology/head and neck surgery. "Cochlear implants are expensive, about $30,000, and it's a difficult procedure for kids to go through."
Shores and Rohlfs plan to test the DNA of the 220 children who have received cochlear implants at UNC. They will begin by looking for mutations in the connexin 26 gene, including the 35delG mutation.
"In terms of learning speech, we know what the outcomes were," Shores said. "There are 30 to 100 different chromosomal sites associated with families that have inherited hearing loss. So far, eight genes have been identified. We'll start with connexin 26 and add other genetic tests as Dr. Rohlfs develops them."
Said Rohlfs: "We'd like to go back through our data base and also look at new patients who come through. There are a lot of different causes of deafness - infectious, environmental, genetic. The general idea is to categorize patients into obvious components, such as infectious disease or genetic, and then to look at the genetic components that we can test. Right now connexin 26 is the one we can test for easily."
Shores points out that hearing loss associated with a connexin 26 mutation is variable. "In a few cases it can be mild but in most it's severe to profound bilateral hearing loss," she says. "But there's some variability even within the same family. In some kids the hearing loss is moderate, in others it's profound."
Rohlfs' UNC collaborators in the connexin frequency study are Dr. Lawrence Silverman, professor of pathology and laboratory medicine, Dr. Jessica Booker, postdoctoral scientist in that department and Dr. Jackie Zhou, research associate in pathology and laboratory medicine. Drs. Harold Pillsbury and Vincent Carrasco are nuero-otologists in the division of otolaryngology/head and neck surgery who perform cochlear implantation.
Other social bookmarking and sharing tools:
The above story is reprinted from materials provided by University Of North Carolina At Chapel Hill School Of Medicine.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Note: If no author is given, the source is cited instead.