The cause of Winchester syndrome was found out half a century after its description
When studying frozen cells isolated from the skin of a girl who died almost 50 years ago, researchers at Mount Sinai Medical School (New York), working under the guidance of Dr. John Martignetti, identified the genetic cause of the so-called Winchester syndrome – a lethal bone disease.
More than half a century ago, Patricia Winchester, a pediatrician-radiologist from New York, was asked to diagnose two sisters suffering from severe progressive arthritis of the fingers and rapid deterioration of mobility of the shoulder, elbow, hip and knee joints as a result of osteoporosis. The girls quickly lost the ability to move independently and soon died.
A photo of one of the girls is shown at the end of the page. For the faint of heart, we recommend not to look at it.
Until recently, the cause of the development of this disease, called "Winchester syndrome", remained a mystery, in an attempt to solve which researchers from Mount Sinai came to the MT1-MMP gene. This gene encodes an enzyme, the correct functioning of which is possible only if it is correctly located in the cell membrane.
The study of the genome of frozen skin cells of one of the girls who died 50 years ago revealed a mutation, due to which the MT1-MMP protein molecules synthesized in the cell did not reach their correct localization in the outer layer of the cell membrane, but got stuck in the cytoplasm. As a result, the enzyme was deprived of the opportunity to interact with the MMP-2 protein, whose anomalies cause a whole group of congenital diseases with similar manifestations – severe arthritis and destruction of bone tissue.
The researchers believe that their discovery will clarify the diagnosis of Winchester syndrome and help in the development of new treatments for children with this and other congenital bone diseases, as well as numerous adults suffering from osteoporosis and arthritis.
Article by Brad R. Evans et al. Mutation of Membrane Type-1 Metalloproteinase, MT1-MMP, Causes the Multicentric Osteolysis and Arthritis Disease Winchester Syndrome is published in the American Journal of Human Genetics.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of Mount Sinai School of Medicine:
Mount Sinai Researchers Solve Mystery Surrounding the Death of Two Sisters Nearly 50 Years Ago.
A snapshot from the article by Winchester et al. A new acid mucopolysaccharidosis with skeletal deformities simulating rheumatoid arthritis (Am J Roentgenol Radium Ther Nucl Med. 1969 May;106(1):121-8: the eldest of the sisters at the age of 8 years.
03.09.2012