WASHINGTON A rare disorder that turns children into old people and often causes them to die in their teens has been linked to a single genetic mutation, a finding that may help science learn more about normal aging as well.
The disorder, called Hutchinson-Gilford progeria syndrome, is caused by a single misspelling'' or misplaced DNA molecule within the human genome that contains some three billion DNA units, said Dr. Francis Collins, head of the National Human Genome Research Institute and the senior author of a report appearing this week in the journal Nature.
Victims of progeria appear normal at birth, but by 18 months begin to develop symptoms of accelerated aging. The skin takes on the appearance of the very old, bones become fragile and most of the children are bald by the age of four. The children never grow much taller than three feet. Their internal organs also quickly age and death is usually caused by heart disease or stroke at an average age of 13.
Even as teenagers, said Dr. W. Ted Brown, the children with progeria will weigh only 30 to 35 pounds.
Children with disorder, however, tend to have above-average intelligence, said Brown, a co-author who has studied progeria for 20 years at the New York State Institution for Basic Research in Development Disabilities.
John Tackett, a 15-year-old from Bay City, Mich., who has progeria, said at the news conference that he was just a regular guy who is very content'' even though he knows his disease is fatal.
Tackett, who stands about three feet high, is a ninth grader who is a whiz at math and an expert pool player. He has a job as a cashier at a Bay City restaurant. But angina, a symptom of advancing heart disease usually seen in people in their 60s and 70s, is already causing him to limit some physical activities. A scarf covered his bald head.
Progeria affects only about one baby per 4 million to 8 million worldwide.
The disease was first identified in 1886, but Brown said it has been difficult to study because there are only a handful or so alive at one time.'' He said about one patient with progeria is born each year in the U.S.
Collins and his co-authors found the mutation on a gene called lamin A in DNA specimens from 18 of 20 progeria patients. A similar study, appearing in the journal Science, found the gene mutation in two progeria patients.
Lamin A, or LMNA, has already been linked to six other diseases. The mutation and the effect is slightly different, on a molecular basis, in each of the diseases.
Linking LMNA to aging, said Collins, means that studying the gene may provide us with a better understanding of what occurs in the body as we all grow older.''
Collins said that disease is not genetically inherited but develops de novo,'' or new, in each patient. He said there is a suggestion that the progeria gene is transferred to the embryo through a flaw in the genes of the father's sperm.
In the study, Collins said researchers looked at the genetic compliment of 20 progeria patients and their parents. He said they found 18 of the patients shared the same mutation in the LMNA gene on Chromosome 1.
The flaw, he said, was a substitution of single DNA base. The amino acid guanine is switched to adenine.
Initially, we could hardly believe that such a small substitution was the culprit,'' said Maria Eriksson, a researcher at the NHGRI and the first author of the study in Nature. How could these bland-looking mutations lead to such terrible consequences?''
Collins said that only recent advances in sequencing of the human genome, or genetic structure, enabled researchers to find the misplaced amino acid.
An international consortium, which includes the NHGRI, announced in mid-April that the human genome has now been sequenced to an accuracy of 99.99 percent and that the whole genome was now available on the Internet.
Collins said that the next step for progeria researchers is to find a drug that corrects the specific flaw from the mutate LMNA gene. Eventually, it may be possible to correct the gene itself, he said.
But Collins said researchers also are going to now look at people who live to be very old see if the is some element of their LMNA gene that makes them resistant to the diseases of aging.
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