Identification of novel genes for x-linked mental retardation / by Marie Mangelsdorf.

Abstract

The aim of this study is to identify novel genes involved in X-linked mental retardation (XLMR). The first part of the project involved molecular characterisation of the breakpoints of three X chromosome rearrangements in three unrelated patients with mental retardation, to identify candidate genes for familial XLMR. The second part involved positional candidate gene screening in a family that was localised to two regions of the X chromosome by linkage analysis and the final part the identification of the homeobox gene ARX and its role in both syndromic and non-syndromic XLMR. This study has addressed the identification of candidate genes for XLMR using two positional cloning approaches and two candidate genes, BGN and TMG3a, have been identified. It has also resulted in a refined linkage interval in a large NSXLMR family, in which screening of candidates has begun. Finally, mutations in the gene ARX have been identified as a significant contributor to the aetiology of XLMR.