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Exome sequencing identifies MUTYH mutations in a family with colorectal cancer and an atypical phenotype
  1. Nuria Seguí1,
  2. Matilde Navarro1,
  3. Marta Pineda1,
  4. Nicole Köger2,
  5. Fernando Bellido1,
  6. Sara González1,
  7. Olga Campos1,
  8. Silvia Iglesias1,
  9. Rafael Valdés-Mas3,
  10. Adriana López-Doriga4,
  11. Marta Gut5,
  12. Ignacio Blanco1,
  13. Conxi Lázaro1,
  14. Gabriel Capellá1,
  15. Xose S Puente3,
  16. Guido Plotz2,
  17. Laura Valle1
  1. 1Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL, Hospitalet de Llobregat, Spain
  2. 2Biomedical Research Laboratory, Medizinische Klinik 1, Universitätsklinikum Frankfurt, Frankfurt, Germany
  3. 3Department of Biochemistry and Molecular Biology, Instituto Universitario de Oncología, Universidad de Oviedo, Oviedo, Spain
  4. 4Unit of Biomarkers and Susceptibility, Catalan Institute of Oncology, IDIBELL and CIBERESP, Hospitalet de Llobregat, Spain
  5. 5Centro Nacional de Análisis Genómico, Fundació Parc Científic de Barcelona, Barcelona, Spain
  1. Correspondence to Dr Laura Valle, Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL, Av. Gran Via 199-203, Hospitalet de Llobregat 08908, Spain; lvalle{at} and to Dr Guido Plotz, Medizinische Klinik 1, Biomedizinisches Forschungslabor, Haus 11, Theodor-Stern-Kai 7, Universitätsklinikum Frankfurt, Frankfurt 60590, Germany; plotz{at}

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Ma et al1 comprehensively assessed the association of previously reported genetic variants with colorectal cancer (CRC) risk. The meta-analyses revealed strong evidence for association with rare MUTYH variants, even when excluding cases with MUTYH-associated polyposis. An article by Nieuwenhuis et al2 accurately defined the phenotypical features of MUTYH-associated polyposis. However, the study was performed on clinic-based series ascertained based on the inheritance model or the presence of polyps, which may miss additional phenotypes relevant to improve the disease characterisation and therefore, its genetic diagnosis. To illustrate this, we report a family with a clinical phenotype that resembled Lynch syndrome but was caused by MUTYH mutations.

To identify novel hereditary CRC genes, we studied an Amsterdam I family (hereditary non-polyposis CRC) with no mutations in the DNA mismatch repair (MMR) genes (figure 1, table 1). By exome sequencing performed on four cancer-affected (II.2, II.6, III.1 and III.6) and one cancer-free (III.5) family members, we identified a total of 11 unreported or rare heterozygous variants present in the cancer-affected individuals (see online supplementary table S1). One of them was MUTYH c.1147delC …

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