Researchers at Cincinnati
Children's Hospital Medical Center have developed the first gene chip to
use in the early diagnosis of at least five hereditary liver diseases, to
detect genetic causes of jaundice in children and adults, and potentially
to lead to personalized treatment options.
The chip, termed the "jaundice chip," is nearly 100 percent effective
in the detection of the most common mutations in children with inherited
causes of jaundice, according to a new Cincinnati Children's study in the
January issue of the journal Gastroenterology.
"Other chips have been developed to assess drug metabolism," said Jorge
Bezerra, MD, a pediatric gastroenterologist at Cincinnati Children's and
the study's lead investigator. "This is the first chip in the world that
has been customized to diagnose genetic mutations in patients with
inherited types of liver diseases."
The chip uses a new technology that rapidly and accurately discloses
the composition of several genes known to cause liver disease in children
and adults. "The jaundice chip may also help us to discover whether subtle
changes in these five genes that can cause devastating diseases in children
may also modify the clinical course of other common liver diseases in
adults," said Mitchell Cohen, M.D., director of the division of
gastroenterology hepatology and nutrition at Cincinnati Children's.
Jaundice is a yellowing of the eyes and skin caused by impairment in
bile flow from the liver to the intestine. Impaired bile flow, or
cholestasis, commonly known as jaundice, can lead to severe liver disease.
In children, jaundice and cirrhosis are responsible for more than half of
the need for liver transplantation.
Previous research on humans identified five genes responsible for
inherited forms of jaundice. Until now, the broad array of causes of
cholestasis including genetic, metabolic, inflammatory and drug- or toxin-
induced disorders, created a challenge for physicians to diagnose a
specific disease. Therefore, the treatment of affected children was not
disease- specific and aimed at optimizing care to help reduce liver
transplantation. With the jaundice chip, however, diagnosis can be
simplified by surveying the genetic code for mutations in specific
diseases.
The jaundice chip was designed as a "five-in-one" gene chip to screen
mutations (a permanent change in the DNA sequence that makes up a gene) in
five genes using only one milliliter, or less than a half of a teaspoon, of
blood. Gene chips contain several thousand small fragments of DNA on a
small piece of glass. Incubation of these chips with the patient's DNA
sample produce chemical signals that "glow" and allow for the detection of
the normal gene sequence, or of mutations if they are present in the
patient.
"The jaundice chip is an extraordinary advance for our patients with
liver diseases. It will improve diagnostic accuracy for perplexing diseases
in infants and children, potentially decrease the need for invasive and
costly studies, and allow us to develop specific treatment plans based on
the correct genetic diagnosis," said Dr. Cohen.
"With further genetic testing of liver disease, there is the potential
that medications can be tailored to meet the needs of individual patients
taking into account the patient's genetic make-up," adds Dr. Bezerra. "For
now, the use of the gene chip gives families piece of mind, knowing what
their child is living with. The next focus of advances will be the
development of medication that may block progression of their disease.
Today, detection of liver diseases with the jaundice chip is
continuing, using samples from children worldwide through a research
protocol in the division of gastroenterology, hepatology and nutrition at
Cincinnati Children's. Once approved by the Food and Drug Administration,
the potential for wider use is limitless, according to Dr. Bezerra.
The discovery of the jaundice chip was made possible through a grant
from the Research Foundation at Cincinnati Children's with additional
support by the National Institutes of Health (NIH).
About Cincinnati Children's Hospital Medical Center
Cincinnati Children's Hospital Medical Center, one of the leading
pediatric research institutions in the nation, is dedicated to changing the
outcome for children throughout the world. Cincinnati Children's ranks
second among all pediatric institutions in the United States in grants from
the National Institutes of Health. It has an established tradition of
research excellence, with discoveries including the Sabin oral polio
vaccine, the surfactant preparation that saves the lives of thousands of
premature infants, and a rotavirus vaccine that saves the lives of hundreds
of thousands of infants around the world each year. Current strategic
directions include the translation of basic laboratory research into the
development of novel therapeutics for the treatment of disease, and
furthering the development of personalized and predictive medicine.
Additional information can be found at cincinnatichildrens.
Cincinnati Children's Hospital Medical Center
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