|
ANN ARBOR,
MI - An international research team, led by University
of Michigan Medical School scientists Marci Lesperance, M.D.,
and Margit Burmeister, Ph.D., has identified a gene responsible
for an unusual type of hearing loss called low frequency sensorineural
hearing loss.
U-M researchers
discovered that children who inherit one copy of the mutated gene
called WFS1 gradually lose their ability to hear low-frequency sounds.
The hearing loss becomes more severe over time, and eventually hearing
aids are required. Patients with different types of mutations affecting
both copies of the gene develop Wolfram Syndrome 1 - a rare, devastating
condition involving juvenile diabetes, optic atrophy, and often
deafness and psychiatric illness.
The wider significance
of this discovery is that mutations in this gene may be a common
cause of low-frequency hearing loss in the general population, even
in those who may be unaware that their hearing loss could be inherited.
Results of
the study appear in the October 22, 2001 issue of Human
Molecular Genetics, published online Nov. 20 at the journal's
web site: http://hmg.oupjournals.org/.
"Discovering
a new gene and its related protein gives scientists another piece
of information to increase their understanding of inner ear development
and function," says Lesperance, an assistant professor of otolaryngology-head
and neck surgery in the U-M Medical School. "These proteins
are produced in tiny amounts in the inner ear or cochlea - an area
that is inaccessible for tissue sampling and difficult to study."
Lesperance's
research team worked closely with Burmeister and Irina Bespalova
of U-M's
Mental Health Research Institute, as well as collaborators at
the University of Antwerp and Rockefeller University, to identify
mutations in six families from the United States and the Netherlands
with a history of low frequency hearing loss.
"Affected
individuals in each family had one of five minor variations called
missense mutations in their WFS1 gene," says Burmeister, an
associate professor of psychiatry and of human genetics in the U-M
Medical School and senior associate research scientist in the U-M
Mental Health Research Institute. "Even though these mutations
changed just one amino acid in the string of 890 amino acids that
make up the protein, it was enough to produce progressive hearing
loss."
One of the
most challenging parts of the study was locating families with this
type of hearing loss. "People who can't hear low-frequency
sounds may not be aware of it, because their ability to understand
speech isn't affected," adds Lesperance. "So it's possible
that this type of hearing loss is more common than we think. Many
people in these families did not know about their hearing loss until
they went to a rock concert and temporarily lost hearing in the
high frequencies, as well."
Lesperance
believes there may be a connection between mutations in WFS1 and
the more common form of progressive sensorineural hearing loss involving
high-frequency sounds like human speech. While family members with
WFS1 mutations had low-frequency hearing loss as children, they
often lost the ability to hear high-frequency sound as they got
older. "High-frequency hearing loss is caused by aging, noise
exposure or drug toxicity, but mutations in WFS1 might make people
more susceptible," she says.
Lesperance
also wants to explore possible involvement of the WFS1 gene in Meniere's
Disease - a common, disabling condition that combines periodic attacks
of low-frequency hearing loss with severe vertigo and tinnitus,
or ringing in the ears.
The study was
funded by the National Institutes of Health, the U-M Biomedical
Research Council, the University of Antwerp and the Flemish FWO,
the Starr Center for Human Genetics and the American Hearing Research
Foundation.
Collaborators
from the University of Michigan included Irina N. Bespalova, Ph.D.,
former research investigator, now an assistant professor of psychiatry
at Mount Sinai School of Medicine; David J. Brown, M.D., house officer
in otolaryngology; Ayse E. Erson, a graduate student in human genetics;
Purnima Kurnool, former research associate; and Theru A. Sivakumaran,
Ph.D., research fellow in otolaryngology. From the University of
Antwerp in Belgium, collaborators included Guy Van Camp, Kim Cryns,
and Kris Flothmann. From the University of Nijmegen in The Netherlands,
they included Steven Bom, Henricus Kunst, and Cor W.R.J. Cremers.
Andrew T. DeWan and Suzanne M. Leal from The Rockefeller University
also collaborated in the study.
For more information
on inherited hearing loss, please see the following web sites:
www.med.umich.edu/childhearinginfo
http://otosclerosis.khri.med.umich.edu
www.khri.med.umich.edu/research/lesperance_lab/index.htm
Written by Sally Pobojewski
For more
information, contact Sally Pobojewski, pobo@umich.edu or Kara
Gavin, kegavin@umich.edu.
Public Relations, 734-764-2220, or by e-mail.
Recent
Press Releases
Return
to Medical School Home Page
|
