A genetic study of neurofibromatosis 1 in south-western Ontario. I. Population, familial segregation of phenotype, and molecular linkage.

This report is concerned with neurofibromatosis type 1 (NF-1, 17q11.2) in south-western Ontario, an ethnically diverse population derived from multiple immigrations. The population incidence, prevalence, and mutation rates for this disease are similar in most racial groups of this population and are also comparable to earlier reports. NF-1 is one of the most common single gene disorders in this population. The occurrence of the disease is not affected by the birth order or sex of the transmitting parent. The severe manifestation of this disease is statistically related to paternal transmission. Five polymorphic DNA probes (pA1041, pHHH202, pTH1719, NF1, pEW206, pEW207) were evaluated in relation to segregation of NF-1 using appropriate restriction enzymes. The observed heterozygosity was found to be relatively high, ranging from 25% to 55% for all the probes on 17q and flanking the NF-1 gene. We recommend the use of pHHH202/pTH1719 and pEW206 in any linkage analysis for detection of the presence of the NF-1 mutation. For informative families the degree of certainty is as high as 99.5%. Some future modifications may include the use of NF-1 exon specific probes and primers that remain to be evaluated for heterogeneity and heterozygosity among populations.