A GENETIC-STUDY OF NEUROFIBROMATOSIS TYPE-1 (NF1) IN SOUTH-WESTERN ONTARIO .2. A PCR BASED APPROACH TO MOLECULAR AND PRENATAL-DIAGNOSIS USING LINKAGE

Neurofibromatosis type 1 (NF1) is a common, autosomal dominant genetic disorder with a variety of highly variable symptoms including cutaneo us manifestations (such as cafe au lait spots), Lisch nodules, plexifo rm neurofibromas, skeletal abnormalities, an increased risk for malign ancy, and the development of learning disabilities. The wide clinical variability of expression of the disease phenotype and high (spontaneo us) mutation rate of the NF1 gene indicate that careful clinical exami nation of patients and family members is necessary to provide an accur ate diagnosis of the disease. Since very few NF1 mutations have been i dentified, and with the apparent lack of a predominant mutation in thi s large, highly mutable gene, molecular diagnosis of NF1 will continue to be based on haplotypes using linkage analysis. Here we report our experiences while providing a molecular diagnostic service for NF1 in the ethnically diverse region of south-western Ontario. Molecular diag noses with at least one informative probe/enzyme combination are repor ted for 19 families including two families requesting prenatal diagnos is for NF1. We have augmented the classical Southern based approach to linkage analysis with the use of PCR based assays for molecular linka ge. Furthermore, criteria have been established in our laboratory for executing molecular linkage based on heterozygosity values, recombinat ion fractions, and the use of intragenic probes markers.