Type and frequency of MUTYH variants in Italian patients with suspected MAP

a retrospective multicenter study

Maria Teresa Ricci, Sara Miccoli, Daniela Turchetti, Davide Bondavalli, Alessandra Viel, Michele Quaia, Elisa Giacomini, Viviana Gismondi, Lupe Sanchez-Mete, Vittoria Stigliano, Aline Martayan, Filomena Mazzei, Margherita Bignami, Luigina Bonelli, Liliana Varesco

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

To determine prevalence, spectrum and genotype-phenotype correlations of MUTYH variants in Italian patients with suspected MAP (MUTYH-associated polyposis), a retrospective analysis was conducted to identify patients who had undergone MUTYH genetic testing from September 2002 to February 2014. Results of genetic testing and patient clinical characteristics were collected (gender, number of polyps, age at polyp diagnosis, presence of colorectal cancer (CRC) and/or other cancers, family data). The presence of large rearrangements of the MUTYH gene was evaluated by Multiplex Ligation-dependent Probe Amplification analysis. In all, 299 patients with colorectal neoplasia were evaluated: 61.2% were males, the median age at polyps or cancer diagnosis was 50 years (16-80 years), 65.2% had <100 polyps and 51.8% had CRC. A total of 36 different MUTYH variants were identified: 13 (36.1%) were classified as pathogenetic, whereas 23 (63.9%) were variants of unknown significance (VUS). Two pathogenetic variants were observed in 78 patients (26.1%). A large homozygous deletion of exon 15 was found in one patient (<1.0%). MAP patients were younger than those with negative MUTYH testing at polyps diagnosis (P<0.0001) and at first cancer diagnosis (P=0.007). MAP patients carrying the p.Glu480del variant presented with a younger age at polyp diagnosis as compared to patients carrying p.Gly396Asp and p.Tyr179Cys variants. A high heterogeneity of MUTYH variants and a high rate of VUS were identified in a cohort of Italian patients with suspected MAP. Genotype-phenotype analysis suggests that the p.Glu480del variant is associated with a severe phenotype.

Original languageEnglish
Pages (from-to)309-315
Number of pages7
JournalJournal of Human Genetics
Volume62
Issue number2
DOIs
Publication statusPublished - Feb 2017

Fingerprint

Multicenter Studies
Retrospective Studies
Polyps
Genetic Testing
Colorectal Neoplasms
Neoplasms
Phenotype
Gene Rearrangement
Multiplex Polymerase Chain Reaction
Genetic Association Studies
Exons
Genotype

Keywords

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Colonic Polyps
  • Colorectal Neoplasms
  • DNA Glycosylases
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Genotype
  • Humans
  • Italy
  • Male
  • Middle Aged
  • Multiplex Polymerase Chain Reaction
  • Mutation
  • Phenotype
  • Retrospective Studies
  • Young Adult
  • Journal Article
  • Multicenter Study

Cite this

Ricci, M. T., Miccoli, S., Turchetti, D., Bondavalli, D., Viel, A., Quaia, M., ... Varesco, L. (2017). Type and frequency of MUTYH variants in Italian patients with suspected MAP: a retrospective multicenter study. Journal of Human Genetics, 62(2), 309-315. https://doi.org/10.1038/jhg.2016.132

Type and frequency of MUTYH variants in Italian patients with suspected MAP : a retrospective multicenter study. / Ricci, Maria Teresa; Miccoli, Sara; Turchetti, Daniela; Bondavalli, Davide; Viel, Alessandra; Quaia, Michele; Giacomini, Elisa; Gismondi, Viviana; Sanchez-Mete, Lupe; Stigliano, Vittoria; Martayan, Aline; Mazzei, Filomena; Bignami, Margherita; Bonelli, Luigina; Varesco, Liliana.

In: Journal of Human Genetics, Vol. 62, No. 2, 02.2017, p. 309-315.

Research output: Contribution to journalArticle

Ricci, MT, Miccoli, S, Turchetti, D, Bondavalli, D, Viel, A, Quaia, M, Giacomini, E, Gismondi, V, Sanchez-Mete, L, Stigliano, V, Martayan, A, Mazzei, F, Bignami, M, Bonelli, L & Varesco, L 2017, 'Type and frequency of MUTYH variants in Italian patients with suspected MAP: a retrospective multicenter study', Journal of Human Genetics, vol. 62, no. 2, pp. 309-315. https://doi.org/10.1038/jhg.2016.132
Ricci, Maria Teresa ; Miccoli, Sara ; Turchetti, Daniela ; Bondavalli, Davide ; Viel, Alessandra ; Quaia, Michele ; Giacomini, Elisa ; Gismondi, Viviana ; Sanchez-Mete, Lupe ; Stigliano, Vittoria ; Martayan, Aline ; Mazzei, Filomena ; Bignami, Margherita ; Bonelli, Luigina ; Varesco, Liliana. / Type and frequency of MUTYH variants in Italian patients with suspected MAP : a retrospective multicenter study. In: Journal of Human Genetics. 2017 ; Vol. 62, No. 2. pp. 309-315.
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