Diagnosi molecolare della Distrofia Muscolare di Duchenne e della Neurofibromatosi tipo 1 con la tecnologia di sequenziamento Next Generation

摘要

Duchenne/Becker muscular dystrophies (DMD/BMD) are the most frequent inherited neuromuscular diseases caused by mutations in the dystrophin gene (DMD). Neurofibromatosis type 1 (NF1), caused by mutations in the neurofibromin gene (NF1), is a multisystem genetic disorder that commonly is associated with cutaneous, neurologic, and orthopedic manifestations. Full characterisation of the mutational spectrum is necessary for genetic counselling, prenatal diagnosis and selecting the patients eligible for future mutation-­‐specific treatments. Identification of the DMD and NF1 point mutations, that account for approximately 30% of DMD and 90% of NF1, cannot be achieved easily because these genes are very large and complex, lacking mutational "hot spots". Next Generation Sequencing (NGS) technology is useful for molecular diagnosis of diseases where laborious sequencing efforts are required. The aim of this study was to work out a method to use the high-­‐throughput NGS technology in a diagnostic settings for Duchenne/Becker muscular dystrophies and Neurofibromatosis type 1. We studied 17 patients (10 DMD and 7 NF1) using the Ion Torrent PGM NGS platform. The results proved that Ion Torrent NGS is suitable for routine clinical practice, with shorter turnaround time, higher accuracy, and better insight into comprehensive genetic information.