Neurofibromatosis type I (NFI) in Israeli families: Linkage analysis as a diagnostic tool

Linkage analysis of 18 neurofibromatosis type I (NFI) families was performed using intragenic and flanking polymorphic markers. The aims of the analysis were prenatal diagnosis of at-risk fetuses, and of asymptomatic individuals who were relatives of NFI patients. Prenatal diagnosis was performed in 9 pregnancies of 7 families; 5 fetuses were diagnosed as affected. In 6 families with an affected spouse, the request was to identify informative polymorphisms to be used in future pregnancies. Presymptomatic diagnosis was performed in 4 families. One individual, a brother of an NFI patient, was found to have Lisch nodules as the only NFI symptom. Linkage analysis indicated that if this person is a carrier of the NFI gene, he must be a product of intragenic crossover. In 2 individuals with a new NFI mutation, the origin of the NFI-bearing chromosomes was paternal. The same observation was noted by others. A summary of published cases shows that some 90% of the NFI-bearing chromosomes of patients with new mutations were of paternal origin. We therefore suggest that for the purpose of prenatal diagnosis in carriers of NFI new (and unidentified) mutations, the paternal chromosome will be considered as the NFI-bearing chromosome. © 1994 Wiley-Liss, Inc.