Oxford Molecular Genetics Laboratory
Genetics Laboratories, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LE
www.ouh.nhs.uk/geneticslab
MutYH Associated Polyposis (MAP) – OMIM #608456, 604933
INTRODUCTION
MAP is an autosomal recessive polyposis predisposition; clinical presentation may be similar to that of attenuated or
classical FAP. It is caused by biallelic mutations in the MUTYH gene, which is involved in base excision repair of DNA
mismatches during DNA replication.
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Two pathogenic variants together account for approximately 73% of MUTYH mutations in the Caucasian population ;
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these are c.536A>G; p.Tyr179Cys (p.Y165C ) in exon 7 and c.1187G>A; p.Gly396Asp (p.G382D ) in exon 13. As
inheritance of the condition is recessive, approximately 53% of affected Caucasian individuals are homozygous or
compound heterozygous for these two variants and ~40% carry one of the variants in addition to a rare mutation. ~7%
MAP patients have neither of these two mutations.
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There is also a founder mutation in the Indian population – c.1438G>T; p.Glu480X (p.E466X ).
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Our mutation numbering is based on accession numbers NM_001128425.1 & NG_008189.1. The A of the ATG (codon 1) is nucleotide number 1.
In accordance with HGVS guidelines we use the largest transcript for mutation nomenclature. This system has not always been in place and
consequently these common mutations are called by a variety of alternatives in the literature (e.g p.Y165C, p.Y176C; p.G382D, p.G393D; p.E466X,
p.E477X respectively)
1: Cheadle and Sampson, 2007, MUTYH-associated polyposis–From defect in base excision repair to clinical genetics testing, DNA Repair, 6:274-9
TESTING
Diagnostic:
Presymptomatic:
Carrier:
Prenatal:
Clinically affected patients
Relatives of individuals in whom MUTYH pathogenic mutations have been identified
who are at risk of developing MAP (for example siblings)
Clinically unaffected individuals at risk of being carriers of MUTYH mutations, for
example relatives of known mutation carriers or affected individuals. Spouses of
mutation carriers may also need carrier testing.
Prenatal testing is not usually requested.
REFERRALS
o All UK diagnostic & presymptomatic/predictive referrals should be referred through Clinical Genetics departments.
o Requests for presymptomatic/predictive testing should either be discussed with the laboratory in advance or be
accompanied by details regarding the pathogenic variant known to be in the family.
o Prenatal requests are only accepted from Clinical Genetics and must be discussed with the laboratory in advance
of sample receipt.
STRATEGY & TECHNICAL INFORMATION
o We routinely test only for the two common Caucasian mutations (p.Tyr179Cys & p.Gly396Asp) and, if requested,
the common Indian/Asian mutation (p.Glu480X). We do not offer an in-house screen of the remainder of the gene
for rare mutations.
o When a pathogenic variant has been identified in an individual, subsequent testing of family members
(presymptomatic or diagnostic confirmation) involves testing for the familial variant only.
TARGET REPORTING TIMES
Diagnostic test:
Presymptomatic/Familial Mutation test:
10 working days
10 working days
N.B. Details are correct for the date of printing only - last updated 11/06/2015