Abstract for presentation at 11th International Congress of Human Genetics

Successes and failures of the GOLD (Genetics of Learning Disability) Service in New South Wales

  • Prof Gillian Turner, NSW GOLD Service, Hunter Genetics, University of Newcastle, Australia
  • Ms Jackie Boyle, NSW GOLD Service, Hunter Genetics, University of Newcastle, Australia
  • A/Prof Jozef Gecz, Dept of Genetic Medicine, Women and Children's Hospital and University of Adelaide, Australia
  • Dr Greg Peters, 3Cytogenetics Department, Western Sydney Genetics Program, Children’s Hospital at Westmead NSW, Australia

    • This program was initiated 20 years ago to identify families with fragile X syndrome through a state wide screening program of the intellectually handicapped. One consequence was finding of many other apparently X linked families (XLMR) who were fragile X negative.In those, where linkage was feasible(LOD>2.0),women at risk were counselled. Generally, diagnosis based on linkage data did not restore reproductive confidence and women tended to opt for no children or foetal sexing. As more genes for XLMR were identified and carrier and non-carrier status could be definitively determined,the attitude of the women in the relevant families changed. Replacement of probability by certainty restored reproductive confidence.
    However,progress has been slow; of the 106 families with confirmed or putative XLMR in our database only ~ 30% have had a mutation identified in some 20 different genes.
    It is becoming clear that the genetic heterogeneity of intellectual disability is considerable, including point mutations in many genes, submicroscopic rearrangements and regulatory mutations. Unravelling these is no simple task and there is no single method,which can detect all types of mutations.
    While in large families linkage information can be used, small families and singletons remain largely unresolved. In the future a prioritised combination of approaches will need to be employed, including re-sequencing (current technology or array based)of multiple candidate genes, array CGH (BAC, SNP or tiling arrays) or routine cytogenetics (inversions) and perhaps expression profiling (for some regulatory mutations) to tackle the enormous task of DNA diagnosis in learning disability.
    We wish to acknowledge our major collaborators Dr Lucy Raymond and the Wellcome Trust-Sanger Institute in Cambridge,England; Prof Hilger Ropers from the Max Planck Institute of Molecular Genetics in Berlin, Germany and the European MRX Consortium for gene identification in our families over the past 5 years.

    Conference Organiser - ICMS Pty Ltd