Novel Lynch syndrome-causing mutation in the MLH1 gene accompanied by a p.R283C mutation in TP53: A case report

Targeted gene panel testing has the power to interrogate hundreds of genes simultaneously and evaluate the genetic risk for many types of hereditary cancers at the same time. Herein, we applied gene panel sequencing and identified a frameshift mutation c.333_334delTC; p.His112CysfsTer9 in the MLH1 gene accompanied by a known missense variant of unknown significance c.847C>T; p.Arg283Cys in the TP53 gene in a young patient with glioblastoma multiforme. The MLH1 variant was also found in the patient's mother, who was diagnosed with breast cancer in the year preceding his diagnosis. To the best of our knowledge, this is the first study reporting the co-occurrence of a Lynch syndrome causing genetic mutation accompanied by a rare functionally relevant variant in the TP53 gene. It is conceivable that the combination of both variants might have a synergistic effect and influence the onset and the tissue specificity of cancer. This report underlines the need for broad panel gene testing in lieu of single-gene or syndrome focused gene screening and evaluation of the effects of multiple pathogenic or modifier variants on the phenotypic spectrum of the disease.