快猫短视频

A MUTATION in a single gene can leave you toothless, according to an
international team who have pinpointed the gene behind a rare gum disease. The
researchers say their finding may help treat more common tooth loss which
affects nearly a third of adults.

People with the genetic disorder Papillon-Lef猫vre syndrome (PLS) lose
all their teeth from gum inflammation, or periodontitis and also get severe
callusing on their hands and feet. Nalin Thakker of the University of Manchester
suspected a flaw in a gene called CTSC might be responsible, because it
codes for an enzyme called cathepsin C that damps down inflammation.

Thakker and his colleagues studied eight families with at least one affected
child and sequenced the CTSC gene from all of them. The team found a
disruptive mutation in both copies of CTSC in the children with PLS,
who had no active cathepsin C enzyme in their blood. Their parents鈥攚ho
each had only one normal copy of the gene鈥攈ad half the normal levels of
the enzyme.

Cathepsin C activates enzymes released by immune cells to attack bacteria,
including those in tooth plaque. It also directs enzymes that dispose of other
immune cells once they have finished killing bacteria鈥攚hich keeps
inflammation at bay. Because PLS sufferers also have heavy callusing on their
palms and feet, Thakker also thinks that cathepsin C helps skin mature properly.
鈥淚f you alter this maturation, you alter the way the gums fit to the teeth,鈥� he
says.

Globally, periodontitis affects 15 per cent of people under 50 and a third of
all adults. Thakker believes that some of these people could have flaws in their
CTSC gene. Although parents with half the normal level of cathepsin C
had no symptoms, a variation in the gene that cut enzyme activity to 10 per cent
might still cause premature tooth loss.

Thakker鈥檚 group is now comparing the CTSC genes of people with
early-onset periodontitis to those of volunteers with healthy teeth. 鈥淣ow that
we understand one of the mechanisms defending the gums,鈥� says Thakker, 鈥渨e may
be able to discover the mechanisms upstream and downstream of cathepsin C.鈥�

CTSC gives researchers an important handle on gum disease, according
to Glen Nuckolls, a specialist in craniofacial development at the National
Institutes of Health near Washington DC. 鈥淟inking a rare disease to a specific
gene can give you insights into more common diseases,鈥� he says.