Nijmegen Breakage Syndrome (NBS)
Summary
Nijmegen breakage syndrome is a chromosomal instability disorder caused by deficiency of nibrin, a protein essential for DNA double-strand break repair. The NBN gene product is part of the MRN complex (MRE11-RAD50-NBS1), a critical sensor and effector of DNA damage responses.
Practical takeaway
Relevant if your partner is of Slavic descent (Polish, Czech, Ukrainian). Carrier testing is available. Realised does not calculate reproductive risk or advise on reproductive decisions.
Evidence detail
What Carrier Status Means For You
You are not affected by NBS. One working copy of NBN produces sufficient nibrin for effective DNA repair. However, some research suggests that NBN 657del5 heterozygous carriers may have a slightly elevated risk of certain cancers (particularly breast cancer), though this association is modest and not fully established. Standard 25/50/25 recessive inheritance applies for NBS itself.
Population Context
The 657del5 variant is a Slavic founder mutation, most common in Poland (~1 in 155), Czech Republic, and Ukraine. Named after the Dutch city of Nijmegen where the syndrome was first described in 1981. Cases have been reported worldwide, predominantly in Slavic populations.
Limitations
23andMe tests 1 NBN variant. Coverage limited to the Slavic founder mutation. Other NBN variants exist but are rare. The carrier cancer risk question remains under investigation.
Sources (4)
- ClinVar: NBN pathogenic/likely pathogenic variant database↗
- OMIM: #251260 (Nijmegen Breakage Syndrome)↗
- Varon et al. (1998), "Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome" — Cell↗
- Cybulski et al. (2004), "NBS1 is a prostate cancer susceptibility gene" — Cancer Research↗