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. Aims: Molecular genetic testing of neurofibromin-1 gene has been performed in our department since 2008; the following report summarizes our experiences. Methods: 40 patients, presenting symptoms of type 1 neurofibromatosis, were screened by sequencing or multiplex ligation-dependent probe amplification. Results: 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. Conclusions: Sequencing of the neurofibromin-1 gene and screening for rearrangements are useful in identifying pathogenic alterations in most of the cases. Orv. Hetil., 2011, 152, 415–419.
The effect of parental age on the presence of de novo mutations – Lessons from neurofibromatosis type I