PMID- 10369266
OWN - NLM
STAT- MEDLINE
DCOM- 19990629
LR  - 20071114
IS  - 1061-4036 (Print)
IS  - 1061-4036 (Linking)
VI  - 22
IP  - 2
DP  - 1999 Jun
TI  - Mutations in the homeodomain of the human SIX3 gene cause holoprosencephaly.
PG  - 196-8
AB  - Holoprosencephaly (HPE) is a common, severe malformation of the brain that
      involves separation of the central nervous system into left and right halves.
      Mild HPE can consist of signs such as a single central incisor, hypotelorism,
      microcephaly, or other craniofacial findings that can be present with or without 
      associated brain malformations. The aetiology of HPE is extremely heterogeneous, 
      with the proposed participation of a minimum of 12 HPE-associated genetic loci as
      well as the causal involvement of specific teratogens acting at the earliest
      stages of neurulation. The HPE2 locus was recently characterized as a 1-Mb
      interval on human chromosome 2p21 that contained a gene associated with HPE. A
      minimal critical region was defined by a set of six overlapping deletions and
      three clustered translocations in HPE patients. We describe here the isolation
      and characterization of the human homeobox-containing SIX3 gene from the HPE2
      minimal critical region (MCR). We show that at least 2 of the HPE-associated
      translocation breakpoints in 2p21 are less than 200 kb from the 5' end of SIX3.
      Mutational analysis has identified four different mutations in the homeodomain of
      SIX3 that are predicted to interfere with transcriptional activation and are
      associated with HPE. We propose that SIX3 is the HPE2 gene, essential for the
      development of the anterior neural plate and eye in humans.
FAU - Wallis, D E
AU  - Wallis DE
AD  - The Children's Hospital of Philadelphia, Department of Pediatrics, University of 
      Pennsylvania School of Medicine, 19104-4399, USA.
FAU - Roessler, E
AU  - Roessler E
FAU - Hehr, U
AU  - Hehr U
FAU - Nanni, L
AU  - Nanni L
FAU - Wiltshire, T
AU  - Wiltshire T
FAU - Richieri-Costa, A
AU  - Richieri-Costa A
FAU - Gillessen-Kaesbach, G
AU  - Gillessen-Kaesbach G
FAU - Zackai, E H
AU  - Zackai EH
FAU - Rommens, J
AU  - Rommens J
FAU - Muenke, M
AU  - Muenke M
LA  - eng
SI  - GENBANK/H84264
SI  - GENBANK/H86855
GR  - HD28732/HD/NICHD NIH HHS/United States
GR  - HD29862/HD/NICHD NIH HHS/United States
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (Eye Proteins)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Sine oculis homeobox homolog 3 protein)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Chickens
MH  - Child, Preschool
MH  - Craniofacial Abnormalities/*genetics
MH  - Eye Proteins
MH  - Female
MH  - Fetus
MH  - *Genes, Homeobox
MH  - Holoprosencephaly/*genetics
MH  - Homeodomain Proteins/*chemistry/*genetics
MH  - Humans
MH  - Infant
MH  - Male
MH  - Mice
MH  - Molecular Sequence Data
MH  - Nerve Tissue Proteins/*chemistry/*genetics
MH  - Pedigree
MH  - *Point Mutation
MH  - Protein Structure, Secondary
MH  - Protein Structure, Tertiary
MH  - Sequence Alignment
MH  - Sequence Homology, Amino Acid
MH  - Xenopus laevis
MH  - Zebrafish
EDAT- 1999/06/16 10:00
MHDA- 2001/03/23 10:01
CRDT- 1999/06/16 10:00
PHST- 1999/06/16 10:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/06/16 10:00 [entrez]
AID - 10.1038/9718 [doi]
PST - ppublish
SO  - Nat Genet. 1999 Jun;22(2):196-8. doi: 10.1038/9718.