THE GENE FOR THE ATAXIA-TELANGIECTASIA VARIANT, NIJMEGEN BREAKAGE SYNDROME, MAPS TO A 1-CM INTERVAL ON CHROMOSOME 8Q21

Nijmegen breakage syndrome (NBS; Seemanova II syndrome) and Berlin bre akage syndrome (BBS), also known as ataxia-telangiectasia variants, ar e two clinically indistinguishable autosomal recessive familial cancer syndromes that share with ataxia-telangiectasia similar cellular, imm unological, and chromosomal but not clinical findings. Classification in NBS and BBS was based on complementation of their hypersensitivity to ionizing radiation in cell-fusion experiments. Recent investigation s have questioned the former classification into two different disease entities, suggesting that NBS/ BBS is caused by mutations in a single radiosensitivity gene. We now have performed a whole-genome screen in 14 NBS/BBS families and have localized the gene for NBS/BBS to a 1-cM interval on chromosome 8q21, between markers D8S271 and D8S270, with a peak LOD score of 6.86 at D8S1811. This marker also shows strong all elic association to both Slavic NBS and German BBS patients, suggestin g the existence of one major mutation of Slavic origin. Since the same allele is seen in both former complementation groups, genetic homogen eity of NBS/BBS can be considered as proved.