Automated comparative sequence analysis identifies mutations in 89% of NF1 patients and confirms a mutation cluster in exons 11–17 distinct from the GAP related domain

Key pointsN Neurofibromatosis type 1 (NF1) is a common auto- somal dominant genetic disorder caused by mutations in the NF1 gene.Mutation detection in NF1 has been a major challenge due to the large size of the gene and lack of mutational hotspots. NWe report here a study on 91 subjects fulfilling the National Institutes of Health (NIH) NF1 diagnostic criteria, in which we achieve a mutation detection rate of 89% using automated comparative sequence analysis (ACSA).This detection rate is the highest for a single technique and is therefore appropriate for routine clinical practice.N Our data show that mutations are evenly distributed along the coding sequence of the NF1 gene and not clustered at the GAP-related domain (GRD).However, we confirm the presence of a second putative functional domain upstream of the GRD at exons 11-17.