Abstract
Nijmegen breakage syndrome is an autosomal recessive disorder caused by biallelic mutation in NBN gene. It is characterized by microcephaly, growth retardation, immuno-deficiency and cancer predisposition. The monoallelic carriers of NBN gene are also reported to be at increased risk of developing various types of malignancy. We have investigated an individual with lung cancer from an extended family segregating different types of hereditary cancer over several generations, including lung, breast, ovarian, colon, prostate and renal cancers. By using next generation whole exome sequencing approach, we identified a rare heterozygous frameshift mutation in NBN gene; c.93_94delTG (Ala32HisfsTer4), which is predicted to be pathogenic together with 3 other variants; 2 being in the BRCA1 gene, c.1648A > C (p.Asn550His) and c.536A > G (p.Tyr179Cys), and one in RAD50 gene, c.3539G > A (p.Arg1180Gln). Some of the variants were also found in six out of eight clinically normal relatives, but in different combinations. To our knowledge, this is the first report of NBN gene mutation in an individual with lung cancer in the Arab world. Reporting such findings may aid in variants’ risk classification and clinical decision in the future.
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We would like to thank the patient and her family for allowing publication of this case report. This work is based on the investigations provided to the patients as part of the free health services that are supported by the Ministry of Health, Kuwait.
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Marafie, M.J., Dashti, M. & Al-Mulla, F. Identification of a rare germline NBN gene mutation by whole exome sequencing in a lung-cancer survivor from a large family with various types of cancer. Familial Cancer 16, 389–394 (2017). https://doi.org/10.1007/s10689-016-9954-9
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DOI: https://doi.org/10.1007/s10689-016-9954-9