Thursday, September 20, 2012
The 80-Year-Old Child
While possessing normal intelligence, affected children develop a distinctive appearance characterized by baldness, aged-looking skin, a pinched nose, and a small face and jaw relative to head size. They also often suffer from symptoms typically seen in much older people: stiffness of joints, hip dislocations and severe, progressive cardiovascular disease. However, various other features associated with the normal aging process, such as cataracts and osteoarthritis, are not seen in children with progeria.
The most severe form of the disease is Hutchinson-Gilford progeria syndrome, recognizing the efforts of Dr. Jonathan Hutchinson, who first described the disease in 1886, and Dr. Hastings Gilford who did the same in 1904.
In 2003, NHGRI researchers, together with colleagues at the Progeria Research Foundation, the New York State Institute for Basic Research in Developmental Disabilities, and the University of Michigan, discovered that Hutchinson-Gilford progeria is caused by a tiny, point mutation in a single gene, known as lamin A (LMNA). Parents and siblings of children with progeria are virtually never affected by the disease. In accordance with this clinical observation, the genetic mutation appears in nearly all instances to occur in the sperm prior to conception. It is remarkable that nearly all cases are found to arise from the substitution of just one base pair among the approximately 25,000 DNA base pairs that make up the LMNA gene.