Page 100 - Genomic Medicine in Emerging Economies

Familial Adenomatous Polyposis 89

these studies (29%–88%), which may be explained by variable selection cri-
teria of patients and technical approaches used for mutation detection. For
example, Cuba reported the lowest percentage of mutations (29%) since their
study was done by heteroduplex technique. On the contrary, when a combi-
nation of SSCP, PTT and Sanger sequencing was used in classic FAP patients
the percentage of mutation carriers rose to 88% (Table 5.5). On average, con-
sidering all studies, 67% of patients have a mutation in APC, but the higher
mutation rate is obtained in patients showing a classic FAP phenotype (79%),
compared to patients with attenuated FAP (40%). Mutations were localized
mainly in exon 15 of APC (82%), specifically between cDNA nucleotides 2486
and 5365 (codon 829 and 1789). This part of the gene includes the “muta-
tional cluster region” described for APC, which includes codon 1309, already
identified as mutated in 19% of Latin American patients. New mutations have
been reported in three publications representing between 36% and 53% of all
mutations detected. The significant rate of novel mutations reported between
studies may be attributed to the scarce information in databases regarding
Latin American patients.
In summary, 76 different mutations have presently been reported until today
for the Latin American population, the majority being point mutations (De
Jesus-Monge et al., 2010), three gene rearrangements involving the deletion
of the APC gene or its partial duplication. For this reason DNA sequencing is
highly effective in the screening of mutations in the FAP patients since only
few patients will need to be studied for gene rearrangements. Finally, seven
mutations are shared between different Latin American countries, two of which
are localized in the hot spots already defined, and present in patients from all
Latin American countries. Among shared mutations we found the following:
c.2626C>T, c.4348 C>T and c.4393_4394delAG present in Brazil and Argen-
tina; c.3783_3784delTT and c.4280delC present in Argentina and Chile; the hot
spot c.3183_3187delACAAA (codon 1061) identified in Argentina, Brazil, Cuba,
Mexico and Puerto Rico; and the hot spot c.3927_3931delAAAGA (codon 1309)
present in Argentina, Brazil, Chile, Cuba, Mexico and Puerto Rico.

MUTYH Associated Polyposis
In 2002, Al-Tassan et al. (2002) determined that some FAP patients with
no mutation in the APC gene have germinal mutation in the MUTYH gene.
This type of polyposis, called MUTYH Associated Polyposis (MAP), was char-
acterized as an autosomic recessive disease with an indistinguishable phe-
notype from FAP, which is caused by mutations in the APC gene (Al-Tassan
et al., 2002; Sampson et al., 2003). The MUTYH gene codes for a DNA gly-
cosylase enzyme that repairs oxidative DNA damages caused by ROS (Oht-
subo, 2000; Cheadle and Sampson, 2003). The more stable oxidized guanine