Mutations in holoprosencephaly

Holoprosencephaly (HPE) is the most common developmental defect of the fore brain and midface in humans. In holoprosencephaly the cerebral hemispheres of the brain fail to separate into distinct left and right hemispheres. Thi s malformation is due to the improper specification and formation of the fo rebrain during early development. When one considers the great number and k inds of genetic interactions that must occur to properly pattern the develo ping forebrain, it is nor surprising that HPE is extremely heterogeneous. I n addition to teratogenic agents, several genes are implicated as the cause of HPE, At least 12 different loci have been associated with HPE and now s everal distinct human genes for holoprosencephaly have been identified. The se genes include Sonic Hedgehog (SHH), ZIC2, SIX3, and TG-interacting facto r (TGIF). Here we present an overview of the presently known genes causing human holoprosencephaly, We discuss their functional role in development of the forebrain and summarize the mutations and polymorphisms that have been identified within them, Hum Mutat 16:99-108, 2000, Published 2000 Wiley Li ss, Inc.dagger.