• PMID: 19105185
• Gene Name: NBN
• Condition: Fertility defects, Nijmegen breakage syndrome (NBS)
• Association: Associated
• Population size: 2
• Population details: 2 siblings with NBS
• Sex: Male, Female
• Infertility type: Male infertility, Female infertility
• Associated genes: NBN
• Other associated phenotypes: Fertility defects, Nijmegen breakage syndrome (NBS)

Fertility defects revealing germline biallelic nonsense NBN mutations

Warcoin M, Lespinasse J, Despouy G, Dubois d'Enghien C, Laugé A, Portnoï MF, Christin-Maitre S, Stoppa-Lyonnet D, Stern MH.

Biallelic mutations in the NBN/NBS1 gene are the cause of Nijmegen breakage syndrome (NBS), a severe pediatric disease characterized by dysmorphy with a bird-like face, microcephaly, growth retardation, immune deficiency, and proneness to cancer. We here report two adult siblings that are compound heterozygotes for two previously unreported NBN nonsense mutations. These patients presented with the unique clinical symptom of fertility defects. Contrasting with the absence of any developmental abnormality, biological analyses revealed defects similar to those observed in NBS patients, including chromosomal instability, cellular hyperradiosensitivity and checkpoint defects as measured by radioresistant DNA synthesis (RDS). NBN mutations should thus be considered a new cause of infertility, and should be searched for if associated with the biological abnormalities of NBS. CI - 2008 Wiley-Liss, Inc. FAU - Warcoin, Mathilde AU - Warcoin M AD - Institut Curie, Centre de Recherche, Paris, France. FAU - Lespinasse, James AU - Lespinasse J FAU - Despouy, Gilles AU - Despouy G FAU - Dubois d'Enghien, Catherine AU - Dubois d'Enghien C FAU - Laugé, Anthony AU - Laugé A FAU - Portnoï, Marie-France AU - Portnoï MF FAU - Christin-Maitre, Sophie AU - Christin-Maitre S FAU - Stoppa-Lyonnet, Dominique AU - Stoppa-Lyonnet D