Frame-shift pathogenic variant in NBNgene in an Iranian family: A case report

Introduction: NBN is a gene found on chromosome ۸ that encodesNibrin protein that is a member of the MRE۱۱/RAD۵۰double-strand break repair complex. Missense mutations, silentmutations, frameshift deletions, and nonsense mutations areobserved in cancers such as colon cancer, stomach cancer, andendometrial cancer.Homologous Mutations in the NBN gene lead to Nijemen breakagesyndrome, which may result in several types of diseases,particularly susceptibility to cancer. Mutation in one copy of theNBN gene leads to impaired DNA repair. The resulting DNAdamage is thought to accumulate over time, which eventuallymay lead into uncontrolled cells proliferation and cancer. NBNis altered in ۲.۲۱% of all invasive ductal carcinoma (IDC) ofbreast, lung adenocarcinoma, colon adenocarcinoma, prostateadenocarcinoma, among which invasive breast carcinoma associateswith the greatest prevalence of alterations.Materials and Methods: We report a ۷۰ year-old male patientwith atypical meningioma of brain. Also, he has strong familyhistory. His brother was diagnosed with skin of eyelid BCC atage ۷۹. His Parents, ۱ uncle and ۶ aunts (father’s sisters andbrother) have gastrointestinal tract cancer. His mother and unclewere affected under ۵۰ years and his aunts in their ۸۰s.Results: Following genetic counselling the family were referredfor Next Generation Sequencing (NGS). The NGS identifiedc.۱۵۷۳delG (p.Asp۵۲۵IlefsTer۴), a frame-shift pathogenicvariant in NBN gene that results in truncated Nibrin protein.Conclusion: Since the NCCN does not outline risk managementguidelines for people with an NBN mutation, additionaldiagnostic experiments were performed to identify the carriersof the mutation among the members of this family The carriershould be alerted about their susceptibility for different types ofcancer. Moreover, avoiding consanguineous marriages and thenecessity of pregestational testing in cases of consanguineousmarriages in prevention of Nijmegen breakage syndrome wasdiscussed with the members of this family.