Germline Mutations Including the Rare Pathogenic Variant c.3206delC in the ATM 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

doi:10.3390/children8060469

Germline Mutations Including the Rare Pathogenic Variant c.3206delC in the ATM Gene Cause Ataxia Teleangiectasia-Associated Primary Central Nervous System Lymphoma

Children (Basel). 2021 Jun 2;8(6):469. doi: 10.3390/children8060469.

Authors

Jan R Dörr^{1

2}, Anne Thorwarth¹, Agnieszka Mizia-Malarz³, Josefine Radke^{2

4

5

6}, Anna Tietze⁷, Pablo Hernáiz-Driever¹, Denise Horn⁸, Alexander Gratopp⁹, Angelika Eggert^{1

2

5

6}, Hedwig E Deubzer^{1

2

5

6

10}

Affiliations

¹ Department of Pediatric Hematology and Oncology, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany.
² Berliner Institut für Gesundheitsforschung (BIH), 10178 Berlin, Germany.
³ Department of Pediatric Oncology, Hematology and Chemotherapy, Upper Silesia Children's Care Health Center, Medical University of Silesia, 40-752 Katowice, Poland.
⁴ Department of Neuropathology, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany.
⁵ German Cancer Consortium (Deutsches Konsortium für Translationale Krebsforschung; DKTK), Partner Site Berlin, 10115 Berlin, Germany.
⁶ German Cancer Research Center Heidelberg (Deutsches Krebsforschungszentrum; DKFZ), 69120 Heidelberg, Germany.
⁷ Department of Neuroradiology, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany.
⁸ Institute of Medical Genetics and Human Genetics, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany.
⁹ Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany.
¹⁰ Experimental and Clinical Research Center (ECRC) of the Charité-Universitätsmedizin Berlin and the Max-Delbrück-Center for Molecular Medicine (MDC) in the Helmholtz Association, 13125 Berlin, Germany.

Abstract

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.

Keywords: cancer; cancer predisposition; chemotherapy tolerance; immune deficiency disorder; multiresistant bacteria.

Publication types

Case Reports