The molecular basis of holoprosencephaly

Jan 19, 2007 13:36 GMT  ·  By

Many monsters encountered in ancient mythologies must have been based on mutated individuals exhibiting weird morphologies.

The Cyclops that Ulysses fought with in Homer's Odyssey might have been based on a rare and strange birth disease named holoprosencephaly. Holoprosencephaly ("one forebrain") appears when the embryonic forebrain swelling fails to divide into the two lobes that later develop into the cerebral hemispheres.

This failure makes the people with this condition present a single-lobed brain cortex and severe skull and facial defects. The disease is extremely severe in most cases, killing the fetuses before birth. When the condition is relatively "mild", babies with near-normal brain development are born, but their faces are affected by eyes, nose, and/or upper lip malformations.

Homer's Cyclops might be a myth, but a disorder that can cause babies to be born with only one eye is very real.

Now a French-American team from Cleveland, Ohio, and Paris, France has made a breakthrough in understanding the molecular basis of one of the molecular causes of this serious birth defect.

In their new research, the scientists explain why and how the embryonic brains fail to divide in two lobes, as how this is connected to skull and facial errors.

This finding will enable better detecting, preventing, and treating this awful disorder.

Holoprosencephaly was found to be triggered by a mutation of the TG interacting factor (TGIF) gene, called TGIF.P63R, which molds brain and skull formation.

The mutation has a double effect: not only does not generate this protein needed for healthy fetal development, but the resulting mutated protein actually destroys the small amounts of the normal protein that is needed. "The name 'Holoprosencephaly' is a mouthful, but the syndrome is awful. This is a devastating condition that has lifelong effects, both for the child and the parents," said Dr. Gerald Weissmann, Editor-in-Chief of The FASEB Journal.

"The new information in this study sheds much-needed light on the complex molecular processes involved in this disorder and allows researchers to identify new areas of intervention."

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