Abstract for presentation at 11th International Congress of Human Genetics

Emerging patterns of cryptic imbalances in patients with idiopathic mental retardation and multiple congenital anomalies: the Leuven experience

  • Dr Thomy de Ravel, Center for Human Genetics, UZ Gasthuisberg, KU Leuven, Belgium
  • Dr Nicole Maas, Center for Human Genetics, UZ Gasthuisberg, KULeuven, Belgium
  • Mr Bernard Thienpont, Center for Human Genetics, UZ Gasthuisberg, KULeuven, Belgium
  • Mr Steve Van Vooren, ESAT-SISTA, KULeuven, Belgium
  • Dr Irina Balikova, Center for Human Genetics, UZ Gasthuisberg, KULeuven, Belgium
  • Prof Jean-Pierre Fryns, Center for Human Genetics, UZ Gasthuisberg, KULeuven, Belgium
  • Prof Koen Devriendt, Center for Human Genetics, UZ Gasthuisberg, KULeuven, Belgium
  • Prof Joris Vermeesch, Center for Human Genetics, UZ Gasthuisberg, KULeuven, Belgium

    • Chromosomal anomalies are a known major cause of mental retardation and multiple congenital anomalies (MR/MCA) and have traditionally been detected in a few percent of patients by standard karyotyping at a 5-10Mb resolution.
    In this study, array CGH at a 1Mb resolution (BAC clone set from Sanger Institute) was performed on 212 selected patients with MR/MCA and normal karyotypes. Suspected microdeletions were verified by FISH and microduplications by real time PCR, and where possible, imbalances were sought in both parents.
    Fifty-one (24%) of the 212 patients had chromosomal imbalances. Microdeletions were detected in 32 patients (15%), microduplications in 15 patients (7%) and a microdeletion as well as a microduplication in 4. Thirty four parent-pairs of the 51 positive patients were tested for carrier status. The origin of the chromosomal imbalance was de novo in 27/34 (79%), maternal in 5 and paternal in 2 patients.
    Interestingly, mosaicism was detected in 3 patients. One had a 12Mb duplication of chromosome 13q in 60% of lymphocytes. The second patient had a 5Mb deletion of chromosome 11q22.1 in all cells, and a duplication of chromosome 11q21-qter in approximately 6% of cultured lymphocytes. The third patient had a monosomy of chromosome 7 in 5-7% of lymphocytes. This clearly illustrates that array CGH detects low grade mosaicism.
    In conclusion, chromosomal imbalances are scattered throughout the genome, both intrachromosomally and telomerically, and with the exception of (mostly) known microdeletion syndromes, are unique. In addition, microdeletions are at least twice as frequent as microduplications (32:15). We recommend routine screening of the patients with MR/MCA with the 1Mb array CGH in view of its high detection rate of chromosomal imbalances.

    Conference Organiser - ICMS Pty Ltd