Research Will Compare Genes of 1,500 Epilepsy Patients
Pa. -- A scientist at the University of Pennsylvania
School of Medicine has been awarded a $2 million federal
research grant for a major study designed to establish
the connection between the most common form of epilepsy
and the way the DNA code may vary in a set of genes
with suspected links to the disease.
Russell Buono, PhD, Research Assistant Professor in
Penn's Department of Psychiatry, will use the grant
from the National Institutes for Health for a four-year
study to compare DNA samples from 1,500 epilepsy patients
with samples from their immediate family members and
from a control group. The DNA will be isolated from
blood collected at sites in Philadelphia and in Ohio.
Buono will be examining the DNA sequences of the suspect
genes to determine whether they can, in fact, be definitively
associated with seizure disorders -- and if they can,
whether those abnormal genes are clustered in particular
"Scientists know that many diseases are caused
by a combination of genetic and environmental factors,"
he said. "It's our belief that subtle variations
in a small number of genes bring about conditions that
predispose individuals for some common forms of seizure
For the nervous system to function properly, and send
out normal electrical impulses, ion channels (which
conduct sodium, potassium, calcium and chloride) must
maintain a balance between the ions inside and outside
nerve cells. Current scientific thinking holds that
seizure disorders result when the ion channels don't
do their job.
Buono's research will encompass juvenile myoclonic epilepsy,
temporal lobe epilepsy and childhood absence epilepsy.
Several of the genes he will study are located on Chromosome
1, which has only recently been associated with temporal
Every year during the study, Buono and his colleagues
will collect 125 DNA samples from patients suffering
from each of the three forms of epilepsy, along with
genetic samples from their parents, siblings or children,
and from a control group -- for a total of 500 DNA samples
from each of the three patient groups and 3,500 from
their close family relatives and controls by the end
of the collection period.
"With that extensive database, we'll be able to
see what genetic variations there may be (in the genes
under study) in people who are affected and then compare
our findings with information from their non-affected
relatives and the control group," Buono said.
"Then, in a follow-up study, we will work to determine
whether any of the genetic variations correlate with
the patients' responses to various anti-convulsant drugs,"
he said. "Our long-term goal is to identify targets
for drug development -- as well as to advance understanding
of the disease itself.
"Establishing a pattern for an illness with such
complex genetic traits is a major challenge," Buono
added. "And it will be doubly challenging because
our study relies on collaboration with so many people
-- physicians, nurses, medical coordinators, technicians,
statisticians, and hundreds of patients and their families."
The DNA material will be collected in Philadelphia at
the the Hospital of the University of Pennsylvania,
Thomas Jefferson University Hospital, and Children's
Hospital of Philadelphia. It will also be collected
at the University of Cincinnati Medical Center and the
Children's Hospital of Cincinnati.
Others collaborating in the study are Wade Berrettini,
MD, PhD; Thomas Ferraro, PhD, and Theresa Scattergood,
RN, MSN, of Penn; Michael R. Sperling, MD, and Michael
J. O'Connor, MD, of Thomas Jefferson Hospital; Michael
Privitera, MD, of the University of Cincinnati, and
Dennis Dlugos, MD, of Childrens Hospital.
Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $6.7 billion enterprise.
The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 20 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $392 million awarded in the 2016 fiscal year.
The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report -- Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.
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