A team of researchers from the University of Nebraska Medical
Center and Boys Town National Research Hospital has located the
gene responsible for Usher syndrome Type IIa — the leading cause
of combined deafness and blindness in the industrialized world.
The discovery, which could lead to an eventual cure for the
genetic disorder, is reported in the June 12 edition of Science.
"This is not only an important step forward in our
understanding of disorders that affect both hearing and vision,
but it will provide further insight into the physiology of vision
and hearing," said Janos Sumegi, D.Sc., M.D., Ph.D.,
professor of pathology/microbiology at UNMC.
About four in 100,000 people suffer from Usher syndrome, a
genetic disorder that causes moderate to severe hearing loss and
the juvenile onset of retinitis pigmentosa — one of the most
common causes of blindness. It was first identified as a genetic
syndrome by a clinician named Charles Usher in 1935. Of the
almost 16,000 deaf and blind people in the United States, more
than half are believed to have Usher syndrome.
During the past 10 years, genetic studies have been conducted
to localize the genes responsible for Usher syndrome. As a
result, three types of the disorder have been identified: Type I,
Type II and Type III. Usher syndrome Type IIa is the most common
type.
The identification of the Type IIa gene is the result of a
collaborative effort during the past six years between Boys Town
National Research Hospital and UNMC. The first step in the gene
identification process was to localize the chromosomal region
where the gene responsible for the genetic disorder is located.
This process was conducted at Boys Town National Research
Hospital under the direction of William Kimberling, Ph.D.,
director of genetic studies, with the help of research associates
Michael Weston, M.S., and Denise Hoover, B.S.
Drs. Kimberling and Sumegi received funding support for this
study through grants from the National Institute of Deafness and
Other Communicative Disorders and the Foundation Fighting
Blindness.
The second step in the gene identification process was the
physical isolation of the gene located on the chromosome 1. This
process was conducted at UNMC by James Eudy, Ph.D., a research
instructor in pathology/microbiology, with the assistance of
Sufang Yao, research technologist in pathology/microbiology,
under the direction of Dr. Sumegi.
Dr. Eudy, who has been working on the project for the past
three years, used a variety of techniques — including DNA
sequencing and computer-based analysis — to isolate the Type IIa
gene.
This is the second gene found to cause Usher syndrome. In
1995, Dr. Kimberling was part of a collaborative research group
credited with finding the gene for Usher syndrome Type I.
Subsequent research studies have found that this gene encodes a
protein called myosin VIIa. This protein is found in both
photoreceptor cells in the retina and in hair cells in the inner
ear. The hair cells have tiny hair-like fibers which help turn
sound waves into electrical impulses that travel to the brain via
the auditory nerve.
Current research under way at UNMC and Boys Town National
Research Hospital is focused on understanding how the Usher
syndrome Type IIa protein functions.
Based upon the similarity of the predicted Usher syndrome Type
IIa protein to other proteins, two hypotheses have been
developed. The first hypothesis suggests that the Type IIa
protein is similar to proteins that form the
"packaging" around the cells, holding them in place and
allowing them to communicate as a group. The second hypothesis
suggests that the Type IIa protein is similar to a receptor — a
protein that spans the cell membrane, communicating the external
environment to the inside of the cell so it can adapt to changing
needs.
The testing of these hypotheses through experimentation will
allow the research team to learn how mutations in the gene cause
deafness and blindness. "We now have the tools to research
the pathology of the disease, which ultimately could lead to a
cure," Dr. Eudy said.