The finding could have significant implications for more common age-related disorders, such as stroke and heart disease, because many Progeria victims die of cardiovascular illness during their teens.
"The cause of Progeria has been found," Dr. Leslie Gordon, co-founder and medical director of the Progeria Research Foundation and the mother of a son with the disease, announced at a news conference in Washington. "This is an exciting and groundbreaking finding," she said.
Finding the gene, Gordon said, "was like trying to find a needle in a haystack."
What scientists at the Progeria Research Foundation and the National Humane Genome Research Institute discovered was a "misspelling" in a gene on chromosome 1 that codes for lamin A, a critical protein responsible for holding the nucleus of a cell intact. By studying 20 children with Progeria, researchers found 18 exhibited the same genetic misspelling.
There are four types of genetic coding that form a gene's base in DNA: cytosine (C), thymine (T), adenine (A), and guanine (G). The misspelling means these 18 children should have had a "C" instead of a "T" on their lamin A-expressing gene.
In a separate study, scientists led by Dr. Nicolas Levy of the Faculte de Medecine de la Timone and the Hopital d'enfants de la Timone in Marseille, France, also made this discovery, which appears in the April 18 issue of the journal Science.
Dr. Francis S. Collins, director of the National Human Genome Research Institute, described the abnormality as a genetic typo that shows up in the male copy of the child's genes, meaning it originated in the father's sperm. However, parents are not genetic carriers of this disease. The condition occurs when a sperm and egg fertilize and begin creating a new genetic life. Progeria is the result of misreading that genetic code from a single sperm.
"It's the one the 'spell-checker' doesn't seem to recognize the most often," Collins told reporters. In essence, he said, the DNA copy machine makes a mistake when creating the DNA of the embryo. "This variation," of just one letter, "alters the splicing of the gene."
Because of that mistake, the lamin A protein becomes defective, causing lamin A proteins to divide improperly and cells to die prematurely.
This, in turn, triggers devastating effects on cells throughout the body. Progeria patients suffer from dwarfism, severe tissue damage in their skeletons, muscles, cardiovascular system, and in their skin. The average age of death is 13, according to the Progeria Research Foundation.
By pinpointing the gene and how it interferes with lamin A, Collins said science has made a big leap toward finding a cure for this disease. "We have a long way to go," Collins said, "but a very exciting path of travel because we have passed through that bottleneck."
Progeria is estimated to affect one in 8 million babies worldwide. The children appear normal at birth, but symptoms such as enlarged head, severe aging of the skin, and musckoskeletal problems develop during the first year. They often die of heart disease or other cardiovascular illnesses during their teens because their heart and bodies are like those of a very elderly person.
John Tackett, a 15-year-old boy from Bay City, Mich., with Progeria and a goodwill ambassador for the Progeria Research Foundation, traveled to Washington for the news conference to express his enthusiasm for this scientific breakthrough.
"This is a very exciting time for me and it should be a very exciting time for my friends," Tackett said. "This is the first step and we're looking forward to the second step."
Collins said the finding could help lead to treatments for heart disease and stroke, which affects millions of people worldwide. Scientists would like to develop a treatment to block this genetic mutation, he said, but they are several steps away from that phase. Currently, scientists are studying people who have reached 100 years to see if they carry some sort of protection in their DNA from this genetic misspelling that causes Progeria.