CF GENE LINKED TO NON-CF INFECTIONS
By Sean Henahan, Access Excellence
CHAPEL HILL, NC (22 August 1997)- A mutated form of the gene
that causes cystic fibrosis also appears to be linked with chronic lung
and sinus infections, report researchers at the University of North Carolina
at Chapel Hill School of Medicine.
"The molecular basis for this genetic mutation -- and I use the term
'mutation' loosely here -- is called the 5T allele, and it appears normally
in 10 percent of the population," said Kenneth Friedman, "Until recently,
the 5T allele was thought to be harmless."
Recent research has shown that the 5T allele is six times more
common in infertile men. Although the men didn't have cystic fibrosis (CF),
they exhibited the same urological abnormalities as men with the illness,
99 percent of whom are infertile.
This led Friedman and colleagues to explore the hypothesis that if the
5T allele can cause one isolated feature of the greater CF disease picture
such as infertility, might it not also be associated with other aspects
of CF-like disease?
The researchers tested a massive data base of DNA samples available
at the UNC School of Medicine's Cystic Fibrosis
Center.
"For many patients with mild sinopulmonary disease, we had never found
CF gene mutations after we'd looked in all the typical places," Friedman
said. "But when we tested their DNA samples for the presence of the 5T
allele, it turned out that the frequency jumped nearly 3-fold. It's more
common among a mixed bag of patients with obscure, hard-to-define lung
and sinus diseases than in the general population."
Individuals with the 5T allele, whether they inherit two copies of the
5T allele or the 5T and a serious CF mutation on the other chromosome,
aren't getting diagnosed anywhere near as early as the typical CF patient,
he said.
"Like CF patients, they may have elevated sweat chloride values (salty
sweat), but their levels aren't nearly as high," he said. "They may
get infections later in life and can be treated with the same antibiotics
as CF patients. In most aspects, they seem to exhibit some sort of milder
form of CF."
The research suggests several promising avenues of investigation. The
researchers now want to find out more about the people who came up positive
for the 5T allele, and determine what they might have in common.
"We need to find out for which clinical syndromes does 5T represent
a genuine risk? If we can find out what these people have in common in
terms of disease then we can do a study where we solicit patients with
those clinical features and see what the 5T allele frequency is among them,"
said Friedman.
Sinusitis seems to be a significant feature of this milder form
of cystic fibrosis, the researcher said. "That's not to say that people
with sinus headaches and allergies should think they have mutations of
the CF gene. That's just not true. It's just that sinusitis can arise from
numerous causes, and one of them might be having the 5T allele. None
of this represents proof. It's an association. The more powerful the association
-- the stronger the statistics -- the more likely it is that the 5T mutation
is the actual cause underlying some milder form of cystic fibrosis."
Cystic fibrosis is the most common fatal genetic illness among whites.
Both men and women can inherit the ailment, and about one in 2,500 whites
are born with it. The median age of survival is 30. The CF gene was cloned
in 1989.
The current findings appear in the August issue of the journal "Human
Mutation."
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