Abstract for presentation at 11th International Congress of Human Genetics

Molecular testing in MAP

  • Ms Shannon Cowie, Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, Australia
  • Mr Steve Nasioulas, Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, Australia
  • Dr Ingrid Winship, Victorian Clinical Genetics Services, Murdoch Childrens Research Institute and Family Cancer Clinic, Royal Melbourne Hospital, Australia
  • Dr Lara Lipton, Family Cancer Clinic, Royal Melbourne Hospital, Australia
  • Dr Elizabeth Chow, Family Cancer Clinic, Royal Melbourne Hospital, Australia
  • Dr Finlay Macrae, Family Cancer Clinic, Royal Melbourne Hospital, Australia
  • Dr Desirée du Sart, Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, Australia

    • The human MutY homologue, MYH, is a human base excision repair gene which encodes a protein of 535 amino acids, involved in the repair of oxidative DNA damage. The MYH gene is located on chromosome 1p32-34 and contains 16 exons. MYH-associated polyposis (MAP) has been described as an autosomal recessive form of FAP, associated with susceptibility to colorectal cancer.
    Studies have identified 2 common missense mutations in the Caucasian population, with amino acid substitutions Y165C and G382D. These mutations have been reported to account for ~82% of mutant alleles. Other mutations have also been identified, some in specific ethnic groups.
    We screened our FAP patient cohort for germline mutations in the MYH gene. All patients had no detectable APC gene mutations after extensive screening which included PTT testing, full gene sequencing and deletion screening. Full MYH-gene sequencing was completed initially on 15 patients. We identified one Y165C homozygote, one G382D homozygote, one compound heterozygote for one common mutation and one rare mutation (G219D/G382D) and one G382D heterozygote. A rapid screening method was then developed to screen 100 patients for the two common Caucasian mutations. We identified one Y165C homozygote, four G382D homozygotes, one compound heterozygote for the two common mutations (Y165C/G382D) and three G382D heterozygotes.
    Full gene sequencing will be performed on patients identified as heterozygotes via the rapid screen, to determine the proportion which are compound heterozygote. As the clinical implications of the heterozygote state are unknown, should full gene sequencing always be completed when one common mutation is identified? Is MAP still a diagnostic possibility when no common mutation is found, or should all patients undergo full gene sequencing?

    Conference Organiser - ICMS Pty Ltd