Lynch syndrome-associated repeated stroke with MLH1 frame-shift mutation.
Mengqi Zhang1, Haojun Yang1, Zhuohui Chen1
1Department of Neurology, Xiangya Hospital of Central South University, Changsha, 410008, Hunan, China.
Summary
Lynch syndrome, a genetic disorder from DNA mismatch repair gene mutations, increases cancer risk. A novel MLH1 mutation was identified in a patient with ovarian cancer and stroke, highlighting the need for genetic testing and prenatal diagnosis.
Area of Science:
- Genetics
- Oncology
- Neurology
Background:
- Lynch syndrome (LS) is an inherited disorder caused by mutations in DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6, PMS2).
- LS predisposes individuals to various cancers, including colorectal, gastric, endometrial, and ovarian cancers.
- Patients with LS have a higher incidence of synchronous and metachronous malignancies.
Observation:
- A 34-year-old female presented with sudden dizziness and left limb weakness.
- Head CT revealed a large infarction in the right frontal temporal parietal lobe and basal ganglia.
- Pathological biopsy confirmed stage IIIA1 high-grade serous ovarian carcinoma (HGSC).
Findings:
- A novel frame-shift mutation (c.1621dupG, p.A541Gfs*16) in the MLH1 gene was identified.
- This mutation likely leads to MLH1 protein dysfunction.
- The mutation correlated with the patient's progressive, multi-system clinical manifestations, including stroke and ovarian cancer.
Implications:
- This case underscores the potential for LS-associated mutations to manifest with diverse and severe symptoms, including neurological events.
- Early identification of novel MMR gene mutations is crucial for understanding LS-related cancer risks.
- Prenatal diagnosis for Lynch syndrome can help prevent new cases of this severe genetic disease.
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