title: Deep sequencing with intronic capture enables identification of an APC exon 10 inversion in a patient with polyposis.
abstract: OBJECTIVE
  Single-exon inversions have rarely been described in clinical syndromes and are challenging to detect using Sanger sequencing. We report the case of a 40-year-old woman with adenomatous colon polyps too numerous to count and who had a complex inversion spanning the entire exon 10 in APC (the gene encoding for adenomatous polyposis coli), causing exon skipping and resulting in a frameshift and premature protein truncation.
  
  
  METHODS
  In this study, we employed complete APC gene sequencing using high-coverage next-generation sequencing by ColoSeq, analysis with BreakDancer and SLOPE software, and confirmatory transcript analysis.
  
  
  RESULTS
  ColoSeq identified a complex small genomic rearrangement consisting of an inversion that results in translational skipping of exon 10 in the APC gene. This mutation would not have been detected by traditional sequencing or gene-dosage methods.
  
  
  CONCLUSIONS
  We report a case of adenomatous polyposis resulting from a complex single-exon inversion. Our report highlights the benefits of large-scale sequencing methods that capture intronic sequences with high enough depth of coverage-as well as the use of informatics tools-to enable detection of small pathogenic structural rearrangements.
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: Brian H
authors.initials: BH
authors.lastname: Shirts
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Salipante
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington, USA.
authors.forename: Silvia
authors.initials: S
authors.lastname: Casadei
authors.affiliation: Providence Health & Services, Spokane, Washington, USA.
authors.forename: Shawnia
authors.initials: S
authors.lastname: Ryan
authors.affiliation: Providence Health & Services, Spokane, Washington, USA.
authors.forename: Judith
authors.initials: J
authors.lastname: Martin
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Jacobson
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: Tatyana
authors.initials: T
authors.lastname: Vlaskin
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Koehler
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Livingston
authors.affiliation: 1] Department of Genome Sciences, University of Washington, Seattle, Washington, USA [2] Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: Mary-Claire
authors.initials: MC
authors.lastname: King
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington, USA.
authors.forename: Tom
authors.initials: T
authors.lastname: Walsh
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: Colin C
authors.initials: CC
authors.lastname: Pritchard
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D000328:Adult; D001483:Base Sequence; D007446:Chromosome Inversion; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D005091:Exons / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D017491:Genes, APC; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D007438:Introns / Q000235:genetics