Found for Rare
Childhood Kidney Disease
(HealthScoutNews) -- After years of searching, researchers have
identified the gene responsible for an rare, inherited kidney
disease that can kill children within days or even hours after
American and Japanese scientists have identified mutations in the
polycystic kidney and hepatic disease 1 (PKHD1) gene both by using
a rat model and by studying the genetic profiles of families with
Previous studies of 16 families with the condition had already
narrowed the search to the sixth human chromosome, but this study
pinpointed the mutation to PKHD1.
The gene has already been sequenced by the Human Genome Project,
and contains the instructions to produce a newly revealed protein
known as fibrocystin. The findings are reported in the March issue
of Nature Genetics.
In polycystic kidney disease (PKD), cysts form on the kidneys,
then gradually fill with fluid, reducing kidney function. The
disease can also interfere with functioning of the liver, heart
and blood vessels in the brain.
Roughly 500,000 Americans have PKD. The autosomal recessive
form of the disease for which the gene was found -- also called
infantile PKD -- is very rare, affecting one in 10,000 children.
A child must inherit a copy of the defective gene from both parents.
It begins in the earliest months of life, sometimes even in the
womb, but some children can live into their teens or 20s.
The disease causes high blood pressure, urinary tract infections
and impaired growth. Although those symptoms can be treated, those
who have the disease may ultimately require kidney dialysis or
Senior investigator Peter Harris, a professor of medicine, biochemistry
and molecular biology at the Mayo Clinic in Rochester, Minn.,
had been studying the autosomal dominant form of the disease that
accounts for 90 percent of PKD cases.
When his researchers learned of a breed of rats from Japan with
characteristics of the recessive form of the disease, they began
to study the animals. Once they found a gene mutation that caused
the rats' version of PKD, they turned to the human genome, expecting
to find that the same gene was responsible for the disease in
Their hunch was correct, and they identified PKHD1 in several
human patients with the recessive form of PKD.
Harris says the most immediate implications of these findings
are in the potential for new ways to diagnose this disease.
"In the longer term, obviously we hope that a better understanding
of what the basic defect is in this disease will enable us to
develop a rational therapy for it," says Harris, although
he cautions that such a development could be years away.
Dr. Tom Coffman, the chief of nephrology at Duke University
Medical Center in Durham, N.C., says the discovery is bound to
create a lot of excitement in the field.
"People have been looking for this gene for a while,"
he says. "It's a real breakthrough in terms of understanding
the genetics of polycystic kidney disease."
Coffman, the author of an accompanying commentary in the journal,
says the combination of studying families with the disease and
animal models of the condition is a "tour de force"
But Coffman cautions that a lot of work remains to be done.
"Applications in molecular diagnostics are potentially possible.
And certainly now that we know the gene, that really provides
a way to direct those sorts of efforts," he says. "But
it's going to be tricky."
In terms of new therapies, he says, the use of the rat model
with the comparable gene mutation may help to develop and test
new therapeutic strategies.
What To Do
For more information on PKD, visit the Web sites for the National
Institute for Diabetes, Digestive and Kidney Diseases, the
Foundation, or the PKD
Reference Source 101