Mutations in the homeodomain of the human SIX3 gene cause holoprosencephaly

摘要: Holoprosencephaly (HPE) is a common, severe malformation of the brain that involves separation central nervous system into left and right halves. Mild HPE can consist signs such as single incisor, hypotelorism, microcephaly, or other craniofacial findings be present with without associated malformations1,2,3. The aetiology extremely heterogeneous, proposed participation minimum 12 HPE-associated genetic loci well causal involvement specific teratogens acting at earliest stages neurulation4. HPE2 locus was recently characterized 1-Mb interval on human chromosome 2p21 contained gene HPE. A minimal critical region defined by set six overlapping deletions three clustered translocations in patients5. We describe here isolation characterization homeobox-containing SIX3 from (MCR). show least 2 translocation breakpoints are less than 200 kb 5´ end SIX3. Mutational analysis has identified four different mutations homeodomain predicted to interfere transcriptional activation propose gene, essential for development anterior neural plate eye humans.