Colorectal - MAP

Question 1

What is MAP?

Answer 1

MUTYH-associated polyposis

Question 2

What is unique about MAPs mode of inheritance?

Answer 2

The first CRC/polyposis with an autosomal recessive inh pattern.

Question 3

What phenotype is associated with MAP?

Answer 3

Similar to AFAP - oligopolyposis (lower number of polyps)

Question 4

What main process is MUTYH involved in?

Answer 4

Base excision repair

Question 5

What is the mutation spectrum of MUYTH?

Answer 5

Predominantly missense (99%).

Two pathogenic variants account for 90% in N. European populations.

Can pre-screen for these first before whole gene screen - finding one only might mean rare variant present elsewhere in gene.

Unaffected partners of affected individuals may be offered screening of these two common variants to help determine risk to offspring.

Question 6

When is MAP suspected?

Answer 6

In APC-negative patients with an AFAP phenotype.

FHx compatible with AR inh can also help distinguish between FAP/MAP.

In reality, would use multi-gene CRC panel incl. APC, MUTYH and others.

Question 7

MAP is AR - is there any risk for heterozygous carriers?

Answer 7

Some evidence suggests heterozygous carriers are at increased risk of CRC compared with the general population.

Question 8

Outside of APC, MUYTH and Lynch genes, are there any other genetic causes of CRC?

Answer 8

Other genes:
- GREM1
- POLD1 / POLE
- STK11 (PJS)
- SMAD4 / BMPR1A (juvenile)
- PTEN
- NTHL1