TGIF1

Nonsyndromic holoprosencephaly

At least 13 mutations in the TGIF1 gene have been found to cause nonsyndromic holoprosencephaly. This condition occurs when the brain fails to divide into two halves (hemispheres) during early development. TGIF1 gene mutations are the fourth most common cause of nonsyndromic holoprosencephaly. These mutations disrupt the protein's ability to bind with DNA or interact with other proteins. As a result, TG-interacting factor cannot block the signals of the TGF-β pathway and retinoic acid. If the signals involved in forebrain development are not properly regulated, the brain does not separate into two hemispheres. The signs and symptoms of nonsyndromic holoprosencephaly are caused by abnormal development of the brain and face.