CONSTITUTIONAL AND MOSAIC LARGE NF1 GENE DELETIONS IN NEUROFIBROMATOSIS TYPE-1

A set of neurofibromatosis type 1 (NF1) patients was screened for larg e NF1 gene deletions by comparing patient and parent genotypes at 10 i ntragenic polymorphic loci. Of 67 patient/parent sets (47 new mutation patients and 20 familial cases), five (7.5%) showed loss of heterozyg osity (LOH), indicative of NF1 gene deletion. These five patients did not have severe NF1 manifestations, mental retardation, or dysmorphic features, in contrast to previous reports of large NF1 deletions. All five deletions were de novo and occurred on the maternal chromosome. H owever, two patients showed partial LOH, consistent with somatic mosai cism. for the deletion, suggesting that mosaicism may be more frequent in NF1 than previously recognised (and may have bearing on clinical s everity), We suggest that large NF1 deletions (1) are not always assoc iated with unusual clinical features, (2) tend to occur more frequentl y on maternal alleles, and (3) are an important mechanism for constitu tional and somatic mutations in NF1 patients.