NEUROFIBROMATOSIS TYPE-I (NFI) IN ISRAELI FAMILIES - LINKAGE ANALYSISAS A DIAGNOSTIC-TOOL

Linkage analysis of 18 neurofibromatosis type I (NFI) families was per formed using intragenic and flanking polymorphic markers. The aims of the analysis were prenatal diagnosis of at-risk fetuses, and of asympt omatic individuals who were relatives of NFI patients. Prenatal diagno sis was performed in 9 pregnancies of 7 families; 5 fetuses were diagn osed as affected. In 6 families with an affected spouse, the request w as to identify informative polymorphisms to be used in future pregnanc ies, Presymptomatic diagnosis was performed in 4 families. One individ ual, a brother of an NFI patient, was found to have Lisch nodules as t he only NFI symptom. Linkage analysis indicated that if this person is a carrier of the NFI gene, he must be a product of intragenic crossov er. In 2 individuals with a new NFI mutation, the origin of the NFI-be aring chromosomes was paternal. The same observation was noted by othe rs. A summary of published cases shows that some 90% of the NFI-bearin g chromosomes of patients with new mutations were of paternal origin. We therefore suggest that for the purpose of prenatal diagnosis in car riers of NFI new (and unidentified) mutations, the paternal chromosome will be considered as the NFI-bearing chromosome. (C) 1994 Wiley-Liss , Inc.