Polymerase proofreading-associated polyposis (PPAP) is an
autosomal dominant
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...
hereditary cancer syndrome, which is characterized by numerous polyps in the colon and an increased risk of
colorectal cancer
Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the Colon (anatomy), colon or rectum (parts of the large intestine). Signs and symptoms may include Lower gastrointestinal ...
.
It is caused by
germline mutation
A germline mutation, or germinal mutation, is any detectable variation within germ cells (cells that, when fully developed, become sperm and Egg cell, ova). Mutations in these cells are the only mutations that can be passed on to offspring, when e ...
s in
DNA polymerase
A DNA polymerase is a member of a family of enzymes that catalyze the synthesis of DNA molecules from nucleoside triphosphates, the molecular precursors of DNA. These enzymes are essential for DNA replication and usually work in groups to create t ...
ε (
POLE) and δ (
POLD1
DNA polymerase delta catalytic subunit (DPOD1) is an enzyme that is encoded in the human by the ''POLD1'' gene, in the DNA polymerase delta complex. DPOD1 is responsible for synthesizing the DNA replication, lagging strand of DNA, and has also be ...
).
Affected individuals develop numerous polyps called
colorectal adenomas. Compared with other polyposis syndromes, Polymerase proofreading-associated polyposis is rare.
Genetic testing
Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or ...
can help exclude similar syndromes, such as
Familial adenomatous polyposis
Familial adenomatous polyposis (FAP) is an autosomal dominant inherited condition in which numerous adenomatous polyps form mainly in the epithelium of the large intestine. While these polyps start out benign, malignant transformation into colon ...
and
MUTYH-associated polyposis.
Endometrial cancer
Endometrial cancer is a cancer that arises from the endometrium (the epithelium, lining of the uterus or womb). It is the result of the abnormal growth of cells (biology), cells that can invade or spread to other parts of the body. The first s ...
, duodenal polyps and
duodenal cancer may also occur.
Genetics
PPAP is an
autosomal dominant
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...
syndrome caused by germline mutations in
DNA polymerase
A DNA polymerase is a member of a family of enzymes that catalyze the synthesis of DNA molecules from nucleoside triphosphates, the molecular precursors of DNA. These enzymes are essential for DNA replication and usually work in groups to create t ...
ε (
POLE) and δ (
POLD1
DNA polymerase delta catalytic subunit (DPOD1) is an enzyme that is encoded in the human by the ''POLD1'' gene, in the DNA polymerase delta complex. DPOD1 is responsible for synthesizing the DNA replication, lagging strand of DNA, and has also be ...
).
The
penetrance
Penetrance in genetics is the proportion of individuals carrying a particular variant (or allele) of a gene (genotype) that also expresses an associated trait (phenotype). In medical genetics, the penetrance of a disease-causing mutation is the pr ...
of the condition appears high.
References
Gastrointestinal cancer
Hereditary cancers
Syndromes affecting the gastrointestinal tract
Autosomal dominant disorders
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