A complex and rare disorder that affects many systems of the body, called oculodentodigital dysplasia, has been found to be the result of faulty cell communication. This syndrome is said to affect various body structures including the eyes, face, teeth and fingers and can also cause hearing loss, heart trouble and neurological problems. A Hopkins-led research team, which studied the genetic samples and medical histories from 17 families with the syndrome, has discovered that changes in a gene called connexin 43 are to blame for the disorder.
Researchers have expressed astonishment at the delay in linking a connexin gene to the disorder which affects so many body systems as connexin 43 and related genes are present in many tissues during development. However, they also add that until now problems with connexins had only been tied to simpler manifestations.
Connexins are a family of roughly 20 genes, best known for creating connections between cells, bridging space called a "gap junction". When connexins on one cell interact with connexins on a neighboring cell, the result is a direct line of communication.
The study involved 17 families in the United States, the Netherlands, Norway and Turkey, and 100 additional people. Scientists suspected the involvement of connexin 43 in the disorder since the gene is turned on in fetal development in a pattern that reflects the problems seen in oculodentodigital dysplasia. They therefore determined the sequence of its building blocks in affected and unaffected members of the 17 families. The researchers reported that only people with the disorder had changes in connexin 43. The researchers also reported that though a different change, or mutation, in the gene was found in each of the 17 families,all changes altered the instructions to make the connexin 43 protein. However, the exact effect of the changes on the protein are yet to be studied.
Scientists suggest that problems with connexin genes (and the proteins made from their instructions) have already been tied to a number of inherited conditions involving deafness or peripheral neuropathy because of their widespread presence in cells during critical developmental periods. Researchers, during the course of this study, have also helped identify a faulty connexin gene as the cause of a skin and deafness disorder known as "KIDS" (for keratitis, ichthyosis and deafness syndrome), while previous findings by others have linked a connexin to Charcot-Marie-Tooth disease.
The researchers concluded that other genes - possibly even other connexins or environmental factors could also account for the variety of effects seen in patients.