Progress towards the isolation and characterization of the genes causing neurofibromatosis.

The locus for the gene causing neurofibromatosis type 1 (NF1) was bracketed to a region on the long arm of chromosome 17 by means of genetic linkage analysis. When the limits of resolution for genetic mapping were reached physical mapping methods were used to map the NF1 gene precisely, with reference to translocation breakpoints in NF1 affected individuals who harboured constitutional chromosomal translocations on chromosome 17. The region of DNA located between two translocation breakpoints has been cloned and a DNA sequence encoding a 11-13 kb mRNA identified. That this sequence shows deletions and point mutations in NF1 affected individuals and not in normal controls provides strong evidence that it is indeed the NF1 gene. The genetic defect in NF2 has been mapped to chromosome 22 by studies of chromosomal loss in tumours associated with this disease. Subsequent linkage analysis of NF2 pedigrees has confirmed this location. DNA markers that bracket the NF2 locus to a region of 5-10 Mb have been identified.