BACKGROUND
Holoprosencephaly (HPE) is a structural anomaly of the brain that arises from either failed or incomplete
forebrain division during the third to fourth week of gestation. There are several types, with alobar HPE being the most severe as there is a monoventricle and no interhemispheric fissure. Single-gene causes of HPE have been linked to TGF β/Nodal signaling, which establishes the left-right patterning in early embryogenesis. Haploinsuffciency of one such gene, TGIF1 (Transforming Growth Factor-Beta-Induced Factor), a co-repressor that limits transcriptional response to TGFβ signaling, leads to dominant holoprosencephaly-4 (OMIM: 142946). Laterality defects, however, have not been associated thus far with TGIF1 loss of function.
