Germline Mutations Including the Rare Pathogenic Variant c.3206delC in the <i>ATM</i> Gene Cause Ataxia Teleangiectasia-Associated Primary Central Nervous System Lymphoma
Jan R. Dörr,
Anne Thorwarth,
Agnieszka Mizia-Malarz,
Josefine Radke,
Anna Tietze,
Pablo Hernáiz-Driever,
Denise Horn,
Alexander Gratopp,
Angelika Eggert,
Hedwig E. Deubzer
Affiliations
Jan R. Dörr
Department of Pediatric Hematology and Oncology, Charité–Universitätsmedizin Berlin, 13353 Berlin, Germany
Anne Thorwarth
Department of Pediatric Hematology and Oncology, Charité–Universitätsmedizin Berlin, 13353 Berlin, Germany
Agnieszka Mizia-Malarz
Department of Pediatric Oncology, Hematology and Chemotherapy, Upper Silesia Children’s Care Health Center, Medical University of Silesia, 40-752 Katowice, Poland
Josefine Radke
Berliner Institut für Gesundheitsforschung (BIH), 10178 Berlin, Germany
Anna Tietze
Department of Neuroradiology, Charité–Universitätsmedizin Berlin, 13353 Berlin, Germany
Pablo Hernáiz-Driever
Department of Pediatric Hematology and Oncology, Charité–Universitätsmedizin Berlin, 13353 Berlin, Germany
Denise Horn
Institute of Medical Genetics and Human Genetics, Charité–Universitätsmedizin Berlin, 13353 Berlin, Germany
Alexander Gratopp
Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité–Universitätsmedizin Berlin, 13353 Berlin, Germany
Angelika Eggert
Department of Pediatric Hematology and Oncology, Charité–Universitätsmedizin Berlin, 13353 Berlin, Germany
Hedwig E. Deubzer
Department of Pediatric Hematology and Oncology, Charité–Universitätsmedizin Berlin, 13353 Berlin, Germany
We here report the case of a 2-year-old patient with a primary central nervous system lymphoma of B-cell origin. Due to their past medical history of repeated respiratory tract infections and the marked chemotherapy-associated toxicity and infectious comorbidity, we suspected that the patient also suffered from an inherited immune deficiency disorder. Despite the lack of classical pathognomonic symptoms for ataxia teleangiectasia and missing evidence for a cancer predisposition syndrome in the family, genetic testing identified biallelic germline mutations, including the rare pathogenic variant c.3206delC (p.Pro1069Leufs*2), in the ataxia telangiectasia-mutated (ATM) gene. The case highlights the importance of searching for immune deficiency disorders associated with primary central nervous system lymphoma before treatment initiation and the urgent need to develop novel treatment strategies for cancer patients with underlying immunodeficiency syndromes.
