Neurofibromatosis: Novel and Recurrent Mutations in Turkish Patients

Neurofibromatosis type 1 is an autosomal-dominant disorder affecting approximately 1 in 3500 births. It is characterized by café-au-lait spots, neurofibromas, axillary/inguinal freckling, and skeletal and neurologic signs. It exhibits full penetrance and a high mutation rate: 50% of neurofibromatosis type 1 patients represent a new mutation. The gene, located at 17q11.2, contains 60 exons that encode a 11-13-kb mRNA transcript. The mutation rate for neurofibromatosis type 1 is one of the highest known for human disorders, probably because of the large size of the gene, gene conversions mediated by pseudogenes, and the presence of repeated sequences. No clear genotype-phenotype correlation is established, except for patients with deletion of the entire neurofibromatosis type 1 gene. Neurofibromatosis type 1 mutations seem to be equally distributed along the gene. However, some exons in the neurofibromatosis type 1 gene may have a higher mutation rate, and the majority of these mutations are recurrent. We analyzed five exons (exons 4b, 16, 29, 31, and 37) for recurrent mutations and unknown mutations in 100 Turkish patients with neurofibromatosis type 1. We identified 496delGT and 499delTGTT mutations in exon 4b and 5866delA as a new mutation in exon 31 (Human Gene Mutation Database accession number Hd0524).