PRESYMPTOMATIC DIAGNOSIS FOR NEUROFIBROMATOSIS-2 WITH CHROMOSOME-22 MARKERS

Neurofibromatosis 2 (NF2) is a dominantly inherited disorder character ized by multiple tumors of the central nervous system, predominantly b ilateral vestibular schwannomas. The gene for NF2 is located in the ch romosomal region 22q12 between the loci D22S1 and D22S28. We have perf ormed genetic linkage analysis on 13 NF2 families with a total of nine polymorphic DNA markers, including five which we have recently mapped to this region. Two loci, D22S32 and NEFH, are linked to the NF2 locu s at 0% recombination (lod scores of 6.03 and 4.28, respectively). By multipoint linkage analysis, we assign the NF2 gene to an interval of 7 cM, between the loci D22S212 and D22S28. We have used this set of ni ne markers to construct chromosome 22 haplotypes for the 82 at-risk in dividuals in this pedigree set. It has been possible to determine, wit h a high degree of certainty, the carrier status of 70 (85%) of these at-risk individuals. Risk prediction was possible in every case where DNA was available from both parents. Fifty-three of the 70 (76%) infor mative individuals were assigned decreased risks of being carriers. Th e use of chromosome 22 probes for risk assessment should result in a g reatly reduced number of individuals who require periodic screening fo r NF2.