NOVEL ALLELES, HEMIZYGOSITY AND DELETIONS AT AN ALU-REPEAT WITHIN THENEUROFIBROMATOSIS TYPE-1 (NF1) GENE

Neurofibromatosis type 1 (NF1) (von Recklinghausen) is a common autoso mal dominant disorder, characterised by the presence of peripheral neu rofibromas, cafe-au-lait spots and Lisch nodules of the iris. Due to t he high mutation rate at the NF1 locus, most patients are expected to have different mutations, limiting molecular analysis and genetic coun seling to the identification of the mutation in each patient or family , or to the use of DNA polymorphisms. We have analysed an Alu-repeat p olymorphic sequence (AAAT), located in intron 27 of the NF1 gene, in 7 0 NF1 and 40 CEPH families and we have detected several genetic and mo lecular abnormalities. In two families the NF1 individuals were hemizy gous at the AAAT-repeat and/or at the CA-repeat of intron 27 of NF1, d ue to interstitial deletions, which include intron 27 to exon 37 of th e NF1 gene. A 71-bp deletion at the Alu sequence was detected in non-N F1 chromosomes of members of three NF1 families. New alleles at the AA AT-repeat were found in one NF1 family and in three CEPH families givi ng a mutation rate for this AAAT-repeat of 0.36% per allele, which is one of the highest detected for a microsatellite locus.