Mutation causes rare gum disease.

In most people, a squadron of enzymes and immune cells works around the clock to keep teeth and gums healthy--even when their host is too busy to brush. For people with Papillon-Lefevre syndrome, however, the teamwork breaks down and healthy gums become an elusive dream. Most lose their permanent teeth in their teens.

These people make a faulty version of cathepsin C, a key player in the gum-protection brigade, an international team of researchers reports in the December NATURE GENETICS. They find that individuals with Papillon-Lefevre syndrome have a mutation on chromosome 11 at the site of the gene, called CTSC, that encodes cathepsin C.

While the full role of this protein remains unknown, the findings establish that an abundance of properly functioning cathepsin C deters infection in the vulnerable spaces where teeth meet gums, says study coauthor Nalin S. Thakker, a dentist and geneticist at St. Mary's Hospital in Manchester, England.

Thakker and his colleagues, including scientists from Egypt and Australia, analyzed blood samples from eight families from Egypt, Pakistan, and Lebanon. Each family has at least one member with Papillon-Lefevre syndrome. Although the parents of affected individuals have reduced cathepsin C activity, none have severe gum disease, or periodontitis, Thakker says.

In each case, however, both parents carried a recessive mutation in CTSC, and the children who had inherited one copy from each parent were burdened with Papillon-Lefevre syndrome. All these parents had married someone within their extended family---often a cousin.

In contrast, the mutations didn't appear at all in 100 Egyptians, 50 Europeans, and 50 South Asians chosen randomly from other families.

Billions of microbes lurk in the mouth, and only a thin layer of skin called the epithelium protects gums from the onslaught. When bacteria lodge between the teeth and gums, many cells in the region make cathepsin C. Also, immune cells called neutrophils rush to the gums.

Thakker and his colleagues investigated cathepsin C because it's necessary for the normal function of neutrophils. He suggests that neutrophils use the protein to activate other enzymes, which fight bacteria. "It would seem logical to conclude that the neutrophils' function is altered in these patients," he says.

The study "helps to further underline the importance of neutrophils in terms of host defense" against periodontitis, says Christopher A. McCulloch of the University of Toronto. Eventually, findings such as these may help scientists devise compounds that make neutrophils more effective at killing bacteria, he adds.

Meanwhile, it remains unclear whether a person's genetic makeup may lead to other types of gum disease, Thakker says. Roughly 15 percent of people lose teeth to periodontitis in middle age.

"Lowered activity of cathepsin C might not cause full-blown Papillon-Lefevre syndrome, but it might cause periodontitis-with less-efficient cleaning up of the plaque bacteria," he says.