ABSTRACT
To establish preclinical DNA-diagnosis of neurofibromatosis type 1 (NF1) in familial cases we have investigated 38 families segregating for the disease. The families were tested with 6 polymorphic DNA markers from the chromosome region 17p11.1-q11.2. Two-thirds of the families were informative for flanking markers. An informative situation was achieved for 33 out of 40 individuals at risk (i.e. first degree relatives): 30 cases were diagnosed as noncarriers of the mutated gene, and three clinically normal individuals (including an adult and two children aged three and six respectively) were found to carry the risk haplotype. The remaining 7 persons at risk could not be typed unequivocally due to non-informative markers or recombination events. In 5 families with healthy grandparents the origin of the mutation could be traced back to the grandfather's germ cells. Despite the recent cloning and initial characterization of parts of NF1 gene, studies using linked and eventually intragenic DNA markers will continue to be of great value for genetic counselling. Such analyses allow highly accurate preclinical and prenatal diagnosis in close relatives of familial cases.
