What specific gene mutations are found in families with suspected Lynch Syndrome?
Lynch Syndrome is a hereditary cancer predisposition syndrome caused by germline mutations in DNA mismatch repair (MMR) genes. These specific genes are MSH2, MSH6, MLH1, and PMS2. Identifying which of these genes is mutated helps doctors understand the specific cancer risks for the family.
What the research says
Research defines Lynch Syndrome as being caused by pathogenic variants in the four DNA mismatch repair genes: MSH2, MSH6, MLH1, and PMS2 2. These mutations are inherited in an autosomal dominant pattern, meaning a person only needs to inherit one altered copy of the gene to have the syndrome 6.
Studies have identified specific types of mutations within these genes. For example, researchers found recurring deleterious mutations in the MLH1 gene among unrelated families, suggesting that certain gene changes are more common in specific populations 6. Other case series have identified specific missense variants and frameshift deletions within the MSH2 gene in families suspected of having the syndrome 3.
When testing is performed, multigene panels can identify mutations in these four MMR genes as well as other cancer predisposition genes. In one large study, about 9% of patients with suspected Lynch Syndrome had a confirmed mutation in one of these primary MMR genes, while others had mutations in different cancer predisposition genes 4.
What to ask your doctor
- Which of the four DNA mismatch repair genes (MLH1, MSH2, MSH6, or PMS2) should I test for first?
- Does my family history suggest a specific mutation that is common in my ancestry?
- What does a 'variant of uncertain significance' mean for my Lynch Syndrome risk?
- Are there specific mutations in my family that have been identified previously?
This question is drawn from common patient questions about Genetics & Precision Medicine and answered using cited medical research. We do not provide individualized advice.