A Novel Nbn Germline Mutation As the Likely Inherited Etiology of Various Cancer Types in an Iranian Family Publisher



Sarmadi A^{1, 2} ; Adelian S³ ; Nouri Z¹ ; Javanmard SH⁴ ; Omidzadeh R⁵ ; Tabatabaiefar MA^{1, 2} Show Affiliations
Source: Egyptian Journal of Medical Human Genetics Published:2025

Abstract

Background: Familial cancer syndromes reflect an inherited tendency to develop benign and malignant tumors. Most patients are diagnosed with cancer at a younger age and include multiple foci of tumor formation in multiple locations. Recently, the molecular basis of many of these cancer syndromes has been revealed with the emergence of powerful genetic technologies. Identification of the genes responsible for familial cancers is just the beginning of a long way into disease mechanisms, preventive measures in the carrier members, and ultimately therapy. Methods: We conducted a clinical examination and molecular genetic testing on a patient with meningioma having a family history of several malignancies. Following WES, many bioinformatics tools were used to evaluate the pathogenicity of the variations, and American College of Medical Genetics and Genomics (ACMG) guidelines were used for its interpretation. Sanger sequencing and co-segregation analysis were performed for the variant’s confirmation. Results: According to WES findings, a novel frameshift heterozygous variation (c.1573delG, p.Asp525llefsTer4) was detected in the NBN gene that causes meningioma in our patient. The pathogenicity of this variant was confirmed based on the ACMG guidelines. It is supposed that this variant is the cause of breast, liver, prostate, and bone marrow cancer in other members of the family. Conclusion: For the first time, we identified a novel disease-causing germline mutation in the NBN gene in a meningioma patient. The detection of pathogenic variants in patients with a high incidence of cancer in their family is beneficial for predicting the prognosis, prenatal diagnosis, and genetic counseling. © The Author(s) 2025.