Case report: a glioma patient diagnosed as constitutional mismatch repair deficiency syndrome (CMMRD) with a de novo germline variant in PMS2

Abstract

Abstract Background Constitutional mismatch repair deficiency syndrome (CMMRD) is a rare autosomal recessive condition caused by biallelic mutations in mismatch repair (MMR) genes. 60% of CMMRD is caused by PMS2. CMMRD is often associated with a higher risk of malignancy in children and adolescents, with brain malignancies accounting for 50% of CMMRD cases. Currently, the diagnosis of CMMRD remains flawed, including immature clinical diagnostic criteria due to the small number of cases, and the complexity and technical limitations of molecular diagnosis. Previously reported CMMRD cases were mainly caused by homozygous mutations in PMS2, and de novo mutations in PMS2 with MSI-H were not reported. Case presentation In our case, we firstly reported a hypermutated glioma patient diagnosed as CMMRD at 22 years old. The patient was identified as CMMRD by the germline result of PMS2 p. V23Ifs*10 LP variant (+ PMS2 p.D694Y VUS variant) based on NGS detection and the clinical phenotype of glioma < 25 years and MSI-H. Conclusions This case sheds light on the limitations of the current diagnosis of CMMRD. Our case focuses on the clinical dilemma of "CMMRD-like" phenotype patients, aiming to attract everyone's attention and actively promote the improvement of CMMRD diagnostic standards.