An AT-rich region in the APC gene may cause misinterpretation of familial adenomatous polyposis molecular screening

Authors

  • Raffaele Palmirotta,

    Corresponding author
    1. Laboratory of Molecular Diagnostics, Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS San Raffaele Pisana, Rome, Italy
    • Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS San Raffaele Pisana, via della Pisana 235, 00163 Rome, Italy
    Search for more papers by this author
  • Maria Laura De Marchis,

    1. Laboratory of Molecular Diagnostics, Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS San Raffaele Pisana, Rome, Italy
    Search for more papers by this author
  • Giorgia Ludovici,

    1. Laboratory of Molecular Diagnostics, Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS San Raffaele Pisana, Rome, Italy
    Search for more papers by this author
  • Barbara Leone,

    1. Laboratory of Molecular Diagnostics, Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS San Raffaele Pisana, Rome, Italy
    Search for more papers by this author
  • Maria Giovanna Valente,

    1. Interinstitutional Multidisciplinary BioBank (BioBIM), Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS San Raffaele Pisana, Rome, Italy
    Search for more papers by this author
  • Jhessica Alessandroni,

    1. Interinstitutional Multidisciplinary BioBank (BioBIM), Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS San Raffaele Pisana, Rome, Italy
    Search for more papers by this author
  • Antonella Spila,

    1. Interinstitutional Multidisciplinary BioBank (BioBIM), Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS San Raffaele Pisana, Rome, Italy
    Search for more papers by this author
  • David Della-Morte,

    1. Interinstitutional Multidisciplinary BioBank (BioBIM), Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS San Raffaele Pisana, Rome, Italy
    2. Department of Neurology, Miller School of Medicine, University of Miami, Miami, Florida
    Search for more papers by this author
  • Fiorella Guadagni

    1. Interinstitutional Multidisciplinary BioBank (BioBIM), Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS San Raffaele Pisana, Rome, Italy
    Search for more papers by this author

  • Communicated by Graham R. Taylor

Abstract

Familial adenomatous polyposis (FAP) is an autosomal-dominant condition mainly due to a mutation of the adenomatous polyposis coli (APC) gene. The present study reports evidence of a technical issue occurring during the mutational analysis of APC exon 4. Genetic conventional direct sequence analysis of a repetitive AT-rich region in the splice acceptor site of APC intron 3 could be misinterpreted as a pathogenetic frameshift result. However, this potential bias may be bypassed adopting a method for random mutagenesis of DNA based on the use of a triphosphate nucleoside analogues mixture. Using this method as a second-level analysis, we also demonstrated the nonpathogenic nature of the variant in the poly A trait in APC exon 4 region (c.423-4delA) that do not result in aberrant splicing of APC exons 3–4; conversely, we did not find a previously reported T deletion/insertion polymorphism. Hum Mutat 33:895–898, 2012. © 2012 Wiley Periodicals, Inc.

Ancillary