Abstract for presentation at 11th International Congress of Human Genetics

Array-CGH: a useful tool to detect and characterise subtelomere abnormalities in patients with intellectual disability

  • Jillian Nicholl, Children,Youth and Women's Health Service, Australia
  • Dr Ashley Connolly, The University of Adelaide, Australia
  • Dr Hong Pan, Children,Youth and Women's Health Service, Australia
  • Mr Paul Nelson, Children,Youth and Women's Health Service, Australia
  • Dr Drago Bratkovic, Children,Youth and Women's Health Service, Australia
  • Dr Eric Haan, Children,Youth and Women's Health Service, Australia
  • Dr Sui Yu, Children,Youth and Women's Health Service, Australia

    • We have constructed a genomic array of 584 clones spanning the last 5Mb of each chromosome end at ~500Kb intervals.Common microdeletion/duplication syndrome regions are also represented. Two different patient groups were evaluated with the array.
    Group 1. Intellectual disability/ developmental delay.
    16 patients were screened. The minimum inclusion criteria were developmental delay or intellectual disability. All patients had a normal karyotype(550 band).
    3 abnormal cases were detected and confirmed by FISH.
    1. A distal 9q duplication in a patient with global delay. The duplication represented 2 clones and is estimated as <1Mb.
    2. A distal 11q duplication in a patient presenting with intellectual disability and strong family history of learning disability. The duplication represented 2 clones and is estimated as < 1Mb.
    3. A duplication of 17p12 in a patient presenting with developmental and speech delay. The duplication represented by 12 clones was estimated to be 3.7Mb.
    Patient screening continues. Parental studies have been requested in all cases, as it is important, particularly with the small duplications to distinguish between changes which are disease-associated from those which are innocuous polymorphisms.
    Group 2. Known cryptic subtelomere abnormalities.
    This array has also been used to map the extent of imbalance in patients with known subtelomeric rearrangements.
    1. In a patient with a de novo 10p deletion, arrayCGH mapped the size of the deletion to be < 0.9Mb, encompassing 4 clones.
    2. In a patient with a de novo 1p deletion, arrayCGH revealed a complex rearrangement. The distal 1p region represented by 17 clones spanning 10Mb indicated three regions of alteration: a distal 2 Mb deletion represented by 4 clones, an interstitial deletion at 6.0-7.0 Mb represented by 2 clones and a duplication of a single clone 8.1 Mb from the telomere. All results were confirmed by FISH. The mechanism of this complex change is under investigation.
    We have demonstrated the usefulness of this array to detect and characterise the extent of chromosome imbalance in patients with intellectual disability or developmental delay, thus facilitating phenotype/genotype associations and gene discovery.

    Conference Organiser - ICMS Pty Ltd