Diagnosis of neurofibromatosis type 1 using RFLPs tightly linked to gene.

This study reports the results of a linkage analysis in nine families with members who had neurofibromatosis type 1 (NF1), using five restriction fragment length polymorphisms (RFLPs) tightly linked to the NF1 locus. The purpose of this analysis was to determine whether the at-risk individuals were carrying the NF1 allele and whether the nine families would be informative for prenatal testing. The families included 25 patients with NF1, 3 individuals at risk for NF1, and 11 unaffected subjects, with a total of 39 family members and 12 matings. In 6 matings two or more flanking probes were informative, in 3 matings only one probe was informative, and in the other 3 no probe was informative. DNA linkage analysis showed with more than 98% probability that the 3 at-risk individuals did not carry the NF1 mutation. No recombination events were observed. In 6 families it will be possible to do a DNA prenatal diagnosis if this type of test is requested. The NF1 gene has been identified and direct testing for the NF1 mutation is now possible. Linkage testing, however, will probably remain useful and complementary to direct analysis of the NF1 gene to reveal intragenic recombination events and for diagnosis in families in which the detection of mutation is difficult.