|Presenting Author(s)||Steven Harvey|
|Abstract Title||The Role of Sall4 in limb development.|
|Full author List||Steven Harvey and Malcolm Logan|
|Text of abstract||
Mutations within the coding region of TBX5 result in Holt-Oram syndrome (HOS) (Li et al., 1997) a disorder characterised by forelimb and heart defects. Typically the left forelimb is more severely affected than the right limb and the most common heart problems are atrial and septal defects (hole in the heart). HOS is a heterogeneous autosomal dominant disorder and although TBX5 mutations result in HOS these have been predicted to only account for ~ 30% of HOS cases (Kohlhase et al., 2002) . Tbx5 is a transcription factor belonging to the T-box gene family, members of which are characterised by the presence of a conserved DNA binding domain - the so-called T-domain. Identification of downstream targets of Tbx5 and factors that interact with Tbx5 could identify genes that when mutated in humans cause HOS-like limb abnormalities.
Mutations within the coding region of SALL4 result in Okihiro syndrome (Kohlhase et al., 2002) . Okihiro syndrome, also called Duane-radial ray syndrome (D.R.R.S., OMIM no. 607323), is an association of forelimbs defects and Duane anomaly - a common eye disorder. The SALL4 mutations described in Okihiro syndrome patients all lead to a premature stop codon within the SALL4 mRNA.
The limb phenotypes of HOS and Okihiro syndrome patients are very similar. As in HOS, Okihiro syndrome patients typically have a more severely affected left forelimb compared to the right. There is also an anterior bias to the limb defects of HOS and Okihiro syndrome patients meaning the thumbs and radius bone are predominantly affected. As well as the phenotypic similarity several HOS patients that lack TBX5 mutations have been demonstrated to contain mutations within the coding region of SALL4 (Brassington et al., 2003) .We have been investigating the role of Sall4 in limb development using zebrafish, chick and mice. We have isolated full-length clones of mouse and zebrafish Sall4. We have also analysed the expression of Sall4 in both species and have begun functional studies in mouse, chick and zebrafish.
|Which session is your work most relevant to:||Human limb abnormalities|
© Copyright 2003 The Medical Research Council Human Genetics Unit
All Rights Reserved