Molecular genetics of holoprosencephaly

Holoprosencephaly (HPE) is a common developmental defect of the human foreb rain and midface. Pathological studies have identified different categories of severity of the brain and craniofacial malformations observed in HPE, a lthough the variable clinical spectrum of HPE extends in unbroken sequence from alobar HPE and cyclopia to clinically unaffected carriers in familial HPE. The etiology of HPE is extremely heterogeneous including both environm ental and genetic causes. Here we focus on molecular aspects of HPE in ligh t of the recent identification of some of the genes causing human HPE and o ther candidate genes involved in forebrain development, through different a pproaches, such as positional cloning and functional cloning, based on anim al models. These approaches will aid in the identification of additional ge nes involved in HPE and in a better understanding of the molecular genetics of brain development.