Mutation spectrum of NF1 gene in Italian patients with neurofibromatosis type 1 using Ion Torrent PGM™ platform

详细信息    查看全文

• 作者：Francesco Calì ; ^a ; ^{cali@oasi.en.it} ; Valeria Chiavetta^a ; Giuseppa Ruggeri^a ; Maria Piccione^b ; Angelo Selicorni^c ; ^d ; Daniela Palazzo^b ; Maria Bonsignore^e ; Anna Cereda^f ; Maurizio Elia^g ; Pinella Failla^g ; Maria Grazia Figura^g ; Agata Fiumara^h ; Silvia Maitz^c ; Giuseppa Maria Luana Mandarà ; ⁱ ; Teresa Mattina^h ; Alda Ragalmuto^a ; Corrado Romano^g ; Martino Ruggieri^h ; Roberto Salluzzo^a ; Antonino Saporoso^e ; Carmelo Schepis^g ; Giovanni Sorge^h ; Maria Spanò ; ^e ; Gaetano Tortorella^e ; Valentino Romano^j
• 关键词：Neurofibromatosis type 1 ; Legius's syndrome ; Next generation sequencing ; Mosaicism
• 刊名：European Journal of Medical Genetics
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：60
• 期：2
• 页码：93-99
• 全文大小：424 K
• 卷排序：60

文摘

Neurofibromatosis type 1 (NF1) is caused by mutations of the NF1 gene and is one of the most common human autosomal dominant disorders. The patient shows different signs on the skin and other organs from early childhood. The best known are six or more café au lait spots, axillary or inguinal freckling, increased risk of developing benign nerve sheath tumours and plexiform neurofibromas. Mutation detection is complex, due to the large gene size, the large variety of mutations and the presence of pseudogenes. Using Ion Torrent PGM™ Platform, 73 mutations were identified in 79 NF1 Italian patients, 51% of which turned out to be novel mutations. Pathogenic status of each variant was classified using “American College of Medical Genetics and Genomics” guidelines criteria, thus enabling the classification of 96% of the variants identified as being pathogenic. The use of Next Generation Sequencing has proven to be effective as for costs, and time for analysis, and it allowed us to identify a patient with NF1 mosaicism. Furthermore, we designed a new approach aimed to quantify the mosaicism percentage using electropherogram of capillary electrophoresis performed on Sanger method.