Analysis of MUTYH Genotypes and Colorectal Phenotypes in Patients With MUTYH-Associated Polyposis

Nielsen, Maartje; Beld, Mirjam C. Joerink van de; Jones, Natalie; Vogt, Stefanie; Tops, Carli M.J.; Vasen, Hans F. A.; Sampson, Julian R.; Aretz, Stefan; Hes, Frederik J.

doi:10.1053/j.gastro.2008.10.056

Cited by 161 publications

(141 citation statements)

References 15 publications

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“…Nevertheless, a robust correlation between certain MUTYH genotypes and the colorectal phenotype has recently been established. 66 Both p.Gly396Asp homozygotes and p.Gly396Asp/ p.Tyr179Cys compound heterozygotes show a later presentation and have a significantly lower CRC hazard than p.Tyr179Cys homozygotes (Po0.001). Interestingly, while the allele frequency in large samples of healthy controls is clearly skewed towards p.Gly396Asp, p.Tyr179Cys dominates in MAP patients (Table 1).…”

Section: Discussionmentioning

confidence: 99%

MUTYH-associated polyposis (MAP): evidence for the origin of the common European mutations p.Tyr179Cys and p.Gly396Asp by founder events

et al. 2013

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MUTYH-associated polyposis (MAP) is an autosomal recessive adenomatous polyposis caused by biallelic germline mutations of the base-excision-repair gene MUTYH. In MAP patients of European origin, the combined allele frequency of the mutations p.Tyr179Cys and p.Gly396Asp ranges between 50 and 82%, while these mutations have not been identified in Far Eastern Asian populations, supporting the hypothesis that a founder effect has occurred at some point in European history. To investigate the natural history of the two common European MUTYH alleles, we genotyped six gene-flanking microsatellite markers in 80 unrelated Italian and German MAP patients segregating one or both mutations and calculated their age in generations (g) by using DMLE þ 2.2 software. Three distinct common haplotypes, one for p.Tyr179Cys and two for p.Gly396Asp, were identified. Estimated mutation ages were 305 g (95% CS: 271-418) for p.Tyr179Cys and 350 g (95% CS: 313-435) for p.Gly396Asp. These results provide evidence for strong founder effects and suggest that the p.Tyr179Cys and p.Gly396Asp mutations derive from ancestors who lived between 5-8 thousand years and 6-9 thousand years B.C., respectively.

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Section: Discussionmentioning

confidence: 99%

MUTYH-associated polyposis (MAP): evidence for the origin of the common European mutations p.Tyr179Cys and p.Gly396Asp by founder events

et al. 2013

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“…Prinzipiell lässt sich auch nach extensivem chirurgischem Vorgehen das Wiederauftreten von Adenomen nicht verhindern [321]. Auch ist derzeit nicht klar, ob die regelmäßige Vorsorgeuntersuchung des Duodenums lebensverlängernd ist [315] [363]. Die Polypen treten im gesamten Dickdarm auf, KRKs finden sich in über 50 % im rechtsseitigen Kolon und in über 20 % im Rektosigmoid [265].…”

Section: Level Of Evidence 1cunclassified

S3-Leitlinie – Kolorektales Karzinom

Schmiegel

Buchberger

Follmann³

et al. 2017

Z Gastroenterol

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“…As such, MAP seems to be a relatively mild form of FAP [Nielsen et al, 2009b]. Biallelic pathogenic MUTYH variants have an estimated penetrance for CRC between $43% and $80% between the ages of 60 and 80 years, with an elevated overall CRC risk of 28-fold [Lubbe et al, 2009].…”

Section: Mutyh-associated Polyposis (Map)mentioning

confidence: 99%