Mutation in Connexin 43 Causes Developmental Disorder

A study has found that mutations in the connexin 43 gene underlie the hereditary syndrome oculodentodigital dysplasia, which is characterized by defects in many of the body's structures and systems, including the eyes, face, teeth, fingers and toes. The study was published January 2, 2003, in the online edition of the American Journal of Human Genetics.

"It is pretty amazing that it has taken so long to link a connexin gene to a disorder that affects so many of the body's systems,” said senior author Dr. Ethylin Jabs, director of the Center for Craniofacial Development and Disorders at Johns Hopkins School of Medicine (Baltimore, MD, USA). "Connexin 43 and related genes are present in many tissues during development, but until now problems with connexins had only been tied to simpler manifestations.”

Connexin 43 was a good candidate for involvement in this developmental disorder, as it was known to play a role in establishing molecular connections between cells. Also, connexin 43 is activated in fetal development in a pattern that reflects the problems seen in oculodentodigital dysplasia.

The investigators determined the sequence of connexin 43 in affected and unaffected members of 17 families in the United States, the Netherlands, Norway, and Turkey and in 100 unrelated people. Only individuals with the disorder had mutations in connexin 43. A different mutation was found in each of the 17 families, but all changes prevented connexin 43 from successfully coding for its protein product.

The authors suggested that their findings should help improve understanding of how connexins contribute to the crucial signaling processes that underlie normal development and may one day lead to a genetic test for families with a history of the disorder.




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