title: Mutation spectrum of NF1 gene in Italian patients with neurofibromatosis type 1 using Ion Torrent PGM™ platform.
abstract: 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.
authors.affiliation: Laboratorio di Genetica Molecolare, UOC Laboratorio di Genetica Medica, Associazione Oasi Maria SS, IRCCS, Troina, EN, Italy. Electronic address: cali@oasi.en.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Calì
authors.affiliation: Laboratorio di Genetica Molecolare, UOC Laboratorio di Genetica Medica, Associazione Oasi Maria SS, IRCCS, Troina, EN, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Chiavetta
authors.affiliation: Laboratorio di Genetica Molecolare, UOC Laboratorio di Genetica Medica, Associazione Oasi Maria SS, IRCCS, Troina, EN, Italy.
authors.forename: Giuseppa
authors.initials: G
authors.lastname: Ruggeri
authors.affiliation: Azienda Ospedali Riuniti Villa Sofia Cervello, Università degli Studi di Palermo, Palermo, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Piccione
authors.affiliation: UOS Genetica Pediatrica, Fondazione MBBM, AOS Gerardo, Monza, Italy; UOC Pediatria ASST Lariana, Como, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Selicorni
authors.affiliation: Azienda Ospedali Riuniti Villa Sofia Cervello, Università degli Studi di Palermo, Palermo, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Palazzo
authors.affiliation: UOC di Neuropsichiatria Infantile, Dipartimento Materno Infantile, Policlinico Universitario "G. Martino", Messina, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Bonsignore
authors.affiliation: UOC Pediatria Ospedale Papa Giovanni XXIII Bergamo, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Cereda
authors.affiliation: Dipartimento per il Ritardo Mentale, Associazione Oasi Maria SS, IRCCS, Troina, EN, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Elia
authors.affiliation: Dipartimento per il Ritardo Mentale, Associazione Oasi Maria SS, IRCCS, Troina, EN, Italy.
authors.forename: Pinella
authors.initials: P
authors.lastname: Failla
authors.affiliation: Dipartimento per il Ritardo Mentale, Associazione Oasi Maria SS, IRCCS, Troina, EN, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Figura
authors.affiliation: Dipartimento di Medicina Clinica e Sperimentale, Sezione di Pediatria e Neuropsichiatria Infantile, Università degli Studi di Catania, Catania, Italy.
authors.forename: Agata
authors.initials: A
authors.lastname: Fiumara
authors.affiliation: UOS Genetica Pediatrica, Fondazione MBBM, AOS Gerardo, Monza, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Maitz
authors.affiliation: UO Genetica Medica, Ospedale Maria Paternò Arezzo, Ragusa, Italy.
authors.forename: Giuseppa Maria
authors.initials: GM
authors.lastname: Luana Mandarà
authors.affiliation: Dipartimento di Medicina Clinica e Sperimentale, Sezione di Pediatria e Neuropsichiatria Infantile, Università degli Studi di Catania, Catania, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Mattina
authors.affiliation: Laboratorio di Genetica Molecolare, UOC Laboratorio di Genetica Medica, Associazione Oasi Maria SS, IRCCS, Troina, EN, Italy.
authors.forename: Alda
authors.initials: A
authors.lastname: Ragalmuto
authors.affiliation: Dipartimento per il Ritardo Mentale, Associazione Oasi Maria SS, IRCCS, Troina, EN, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Romano
authors.affiliation: Dipartimento di Medicina Clinica e Sperimentale, Sezione di Pediatria e Neuropsichiatria Infantile, Università degli Studi di Catania, Catania, Italy.
authors.forename: Martino
authors.initials: M
authors.lastname: Ruggieri
authors.affiliation: Laboratorio di Genetica Molecolare, UOC Laboratorio di Genetica Medica, Associazione Oasi Maria SS, IRCCS, Troina, EN, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Salluzzo
authors.affiliation: UOC di Neuropsichiatria Infantile, Dipartimento Materno Infantile, Policlinico Universitario "G. Martino", Messina, Italy.
authors.forename: Antonino
authors.initials: A
authors.lastname: Saporoso
authors.affiliation: Dipartimento per il Ritardo Mentale, Associazione Oasi Maria SS, IRCCS, Troina, EN, Italy.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Schepis
authors.affiliation: Dipartimento di Medicina Clinica e Sperimentale, Sezione di Pediatria e Neuropsichiatria Infantile, Università degli Studi di Catania, Catania, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sorge
authors.affiliation: UOC di Neuropsichiatria Infantile, Dipartimento Materno Infantile, Policlinico Universitario "G. Martino", Messina, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Spanò
authors.affiliation: UOC di Neuropsichiatria Infantile, Dipartimento Materno Infantile, Policlinico Universitario "G. Martino", Messina, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Tortorella
authors.affiliation: Dipartimento di Fisica e Chimica, Università degli Studi di Palermo, Palermo, Italy.
authors.forename: Valentino
authors.initials: V
authors.lastname: Romano
mesh_terms: D000293:Adolescent; D000328:Adult; D019080:Cafe-au-Lait Spots / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007223:Infant; D007558:Italy; D008297:Male; D008875:Middle Aged; D009030:Mosaicism; D009154:Mutation; D009456:Neurofibromatosis 1 / Q000235:genetics* / Q000473:pathology; D025542:Neurofibromin 1 / Q000235:genetics*; D017422:Sequence Analysis, DNA; D012868:Skin Abnormalities / Q000235:genetics* / Q000473:pathology
chemical_list: D025542:Neurofibromin 1
keywords: Legius's syndrome; Mosaicism; Neurofibromatosis type 1; Next generation sequencing