First Report of Glioblastoma and Associated PNKP Mutation

Background/Purpose: Patients with polynucleotide kinase-3'-phosphatase (PNKP) mutation are characterized by microcephaly, seizures and developmental delay. PNKP enables neurogenesis via multiple DNA repair pathways to maintain genome stability and is essential for glial homeostasis. Concerning the pathophysiological understanding, a predisposition for malignancies is suspected; however it lacks at reports of related tumours.

Methods: A literature review was performed. The case report was worked up by retro-perspective analysis of the patient's health records.

Results: A 4-year-old boy presented at our emergency department because of increased seizure frequency and vomiting. Furthermore, a neurodevelopmental delay, microcephaly, epilepsy and homozygous PNKP germline mutation was known.

MR imaging revealed a massive intracranial tumor in left frontal lobe with midline shift and tonsillar herniation. Histopathological examination after microsurgical resection confirms a glioblastoma with NRAS and TP53 mutation. After 2 weeks, surgical resection was performed again, due to tumor growth. However, the tumor kept on growing aggressively and epilepsy became refractory. Due to these condition, palliative treatment was provided, later the patient died of the illness. This is the first documented case of glioblastoma and associated PNKP mutation.

Conclusion: Routinely examination on PNKP-mutation in glioblastoma and other malignancies is not established. This case indicates importance on further exploration of PNKP variants, which might play an underrated role in brain-tumor genesis and other malignancies.

Publication History

Article published online:
28 October 2021