title: Breakpoint characterization of a novel large intragenic deletion of MUTYH detected in a MAP patient: case report.
abstract: BACKGROUND
  MUTYH-associated polyposis (MAP) is a recessive, hereditary, colorectal cancer-predisposing syndrome caused by biallelic mutations in the MUTYH gene. Most MUTYH pathogenic variants are missense mutations, and until recently no gross genomic deletions had been described.
  
  
  METHODS
  We have identified a large deletion in the MUTYH gene: a > 4.2 kb deletion encompassing exons 4-16. This is the second description of this rearrangement, which has been recently described as the first large deletion in this gene. The clinically suspected MAP patient was homozygous for this mutation and presented with no amplification products for 14 exons of MUTYH on initial screening. Deletion breakpoints were refined to base pair level through array comparative genomic hybridization (aCGH) analysis followed by sequencing. The identified breakpoints were located within intron 3 and 146 bp downstream of the 3' end of the gene, with the presence of an AluJr element adjacent to the distal breakpoint. The presence of a 2 bp insertion at the junction suggests the involvement of the non-homologous end joining (NHEJ) repair mechanism, possibly facilitated by rearrangement-promoting elements. Examination of the MUTYH locus revealed a high Alu density that may make this region prone to rearrangements.
  
  
  CONCLUSIONS
  Large deletions are a possible mechanism for loss of function of the MUTYH gene, and investigation of such mutations may be important in identifying causative mutations in MAP patients.
authors.affiliation: International Center of Research and Training (CIPE), A, C, Camargo Hospital, São Paulo, SP, Brazil.
authors.forename: Giovana T
authors.initials: GT
authors.lastname: Torrezan
authors.forename: Felipe C C
authors.initials: FC
authors.lastname: da Silva
authors.forename: Ana C V
authors.initials: AC
authors.lastname: Krepischi
authors.forename: Érika M M
authors.initials: ÉM
authors.lastname: Santos
authors.forename: Fábio de O
authors.initials: Fde O
authors.lastname: Ferreira
authors.forename: Benedito M
authors.initials: BM
authors.lastname: Rossi
authors.forename: Dirce M
authors.initials: DM
authors.lastname: Carraro
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D020087:Alu Elements / Q000235:genetics; D001483:Base Sequence; D055028:Comparative Genomic Hybridization; D045647:DNA Glycosylases / Q000235:genetics*; D005091:Exons; D005260:Female; D006720:Homozygote; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D012004:Rectal Neoplasms / Q000235:genetics; D017384:Sequence Deletion
chemical_list: D045647:DNA Glycosylases; C061738:mutY adenine glycosylase