Research Information System
American Journal of Medical Genetics, Part A, vol.197, no.11, 2025 (SCI-Expanded)
Nijmegen breakage syndrome (NBS, MIM #251260) is a rare DNA repair disorder characterized by microcephaly, growth retardation, dysmorphic features, hypergonadotropic hypogonadism, immunodeficiency, and predisposition to cancer. NBS results from biallelic pathogenic variants, predominantly truncating in the NBN gene, which plays a role in the homologous recombination pathway. Some variant/atypical clinical presentations in DNA repair disorders have been reported in the literature, and they are associated with hypomorphic variants. To date, only seven patients with mild NBS have been reported in the literature. Herein, we describe a new elderly patient with prostate cancer carrying a homozygous NM_002485.5:c.2140C>T (p.Arg714Ter) variant in the NBN gene without apparent syndromic features of Nijmegen breakage syndrome. Based on our knowledge, our patient is the oldest documented individual with a pathogenic biallelic NBN variant. This patient is distinct from the other mild NBS patients in his fertility, chromosomal analysis, personal cancer history, and skin lesions. Considering the other previously reported patients with mild NBS in the literature, beyond the NBN-related infertility phenotype, it can be suggested that an attenuated form of NBN-related NBS may exist, possibly due to hypomorphic variants. This report aims to broaden our understanding of this rare phenotype and the clinical spectrum of the syndrome.