Case report: A germline leads to a splicing error in a family with multiple cancer patients.

BACKGROUND

Genome instability plays a crucial role in promoting tumor development. Germline mutations in genes responsible for DNA repair are often associated with familial cancer syndromes. A noticeable exception is the gene. Despite its well-established role in homologous recombination, germline mutations in are rarely reported.

CASE PRESENTATION

In this report, we present a patient diagnosed with ovarian clear cell carcinoma who has a family history of cancer. Her relatives include a grandfather with esophageal cancer, a father with gastric cancer, and an uncle with a brain tumor. The patient carried a typical genomic profile of clear cell carcinoma including mutations in , , and . Importantly, her paired peripheral blood cells harbored a germline mutation, , which was also found in her father. Unfortunately, the status of her grandfather and uncle remains unknown due to the unavailability of their specimens. Further evaluation via RT-PCR confirmed a splicing error in the gene, resulting in truncation at the kinase domain region, indicative of a loss-of-function mutation.

CONCLUSION

This case highlights a rare germline mutation within a family with a history of cancer. The confirmed splicing error at the mRNA level underscores the functional consequences of this mutation. Documenting such cases is vital for future evaluation of inheritance patterns, clinical penetrance of the mutation, and its association with specific cancer types.