Abstract for presentation at 11th International Congress of Human Genetics

Subtelomeric Testing by Multiplex Ligation – dependent Probe Amplification (MLPA) in a Diagnostic Setting

  • Ms Kathy Cox, Department of Genetic Medicine, Women's and Children's Hospital, Adelaide, Australia
  • Jillian Nicholl, Department of Genetic Medicine, Women's and Children's Hospital, Adelaide, Australia
  • Sharon Bain, Department of Genetic Medicine, Women's and Children's Hospital, Adelaide, Australia
  • Trudy Hocking, Department of Genetic Medicine, Women's and Children's Hospital, Adelaide, Australia
  • Sarah Smith, Department of Genetic Medicine, Women's and Children's Hospital, Adelaide, Australia
  • Rebecca Buchheim, Department of Genetic Medicine, Women's and Children's Hospital, Adelaide, Australia
  • Prof Eric Haan, Department of Genetic Medicine, Women's and Children's Hospital, Adelaide, Australia
  • Dr Sui Yu, Department of Genetic Medicine, Women's and Children's Hospital, Adelaide, Australia

    • Subtelomeric rearrangements are responsible for 5-7% of cases of idiopathic mental retardation (MR)/developmental delay (DD). Until now, methods for the detection of these abnormalities have been complex and expensive; therefore they have been limited to carefully selected patients. We have recently incorporated MLPA subtelomeric testing into our diagnostic laboratory to screen for subtelomeric aberrations in patients with idiopathic MR/DD. Patients were referred by clinical geneticists, neurologists and general practitioners. All patients had a normal karyotype at the 550 band level.
    We have screened 260 patients for subtelomeric aberrations using two different MLPA kits (SALSA P036B/PO69 MRC – Holland).
    We have detected 11 patients (4.2%) with subtelomeric aberrations who can be divided into two groups. The first group includes five patients (1.9%) with aberrations detected using both subtelomere MLPA kits - 4 patients with a deletion (4q-, 10p- and 1p- in 2 patients) and 1 patient with an unbalanced familial t(15;17). All anomalies were confirmed by FISH.
    The second group includes six patients (2.3%) with an abnormal result in only one of the two MLPA kits used. These include 12q- (P036B), 15q- (P069) in 2 cases, 15p- paracentric (P036B), 22q- (P036B) and a 10q+ (P036B). Where possible, we have tested parental DNA to determine if the change is likely to be a polymorphism or a pathogenic mutation. In patients within this group where a deletion has been detected, we will be presenting the sequencing results of the MLPA target region to determine if a single nucleotide polymorphism (SNP) within the probe target region is responsible.
    Confirming other previous reports, we have seen a relatively high frequency of subtelomeric abnormalities (minimum of 1.9%) within our unselected patients with MR. This study supports the use of MLPA in routine subtelomere screening in patients with MR/DD.

    Conference Organiser - ICMS Pty Ltd