Molecular genetic diagnosis of neurofibromatosis type I

Type 1 neurofibromatosis is an autosomal dominant hamartosis, caused by mutations of the gene neurofibromin-1. The variable clinical phenotype is characterized by café-au-lait spots, benign neurofibromas, axillary, inguinal hyperpigmentations, iris hamartomas, skeletal deformities and risk of neurofibroma-development. Pathogenic variations of neurofibromin-1 arise as de novo mutations in approx. 50% of the cases.Molecular genetic testing of neurofibromin-1 gene has been performed in our department since 2008; the following report summarizes our experiences.40 patients, presenting symptoms of type 1 neurofibromatosis, were screened by sequencing or multiplex ligation-dependent probe amplification.Pathogenic alterations were identified in 31 cases, 8 patients presented novel mutations. In 8 affected, no mutations were detected by sequencing; one of these patients had a deletion affecting the entire gene.Sequencing of the neurofibromin-1 gene and screening for rearrangements are useful in identifying pathogenic alterations in most of the cases.