The severe malformations exhibited in the cranial fossae, orbital region, pituitary gland and sella turcica highlight the crucial involvement of transcription factors such as TGIF, which is located on chromosome 18 and contributes to neural patterning, in the proper development of neural and cranial structures.
Loss of function mutations in a single copy of TGIF result in holoprosencephaly, a developmental anomaly leading to severe forebrain and craniofacial malformations.
Heterozygous nonsense and missense mutations of the human TGIF gene have been associated with holoprosencephaly, the most common congenital malformation of the forebrain.