TY - JOUR
T1 - The Genetic Landscape of Dystrophin Mutations in Italy
T2 - A Nationwide Study
AU - Neri, Marcella
AU - Rossi, Rachele
AU - Trabanelli, Cecilia
AU - Mauro, Antonio
AU - Selvatici, Rita
AU - Falzarano, Maria Sofia
AU - Spedicato, Noemi
AU - Margutti, Alice
AU - Rimessi, Paola
AU - Fortunato, Fernanda
AU - Fabris, Marina
AU - Gualandi, Francesca
AU - Comi, Giacomo
AU - Tedeschi, Silvana
AU - Seia, Manuela
AU - Fiorillo, Chiara
AU - Traverso, Monica
AU - Bruno, Claudio
AU - Giardina, Emiliano
AU - Piemontese, Maria Rosaria
AU - Merla, Giuseppe
AU - Cau, Milena
AU - Marica, Monica
AU - Scuderi, Carmela
AU - Borgione, Eugenia
AU - Tessa, Alessandra
AU - Astrea, Guia
AU - Santorelli, Filippo Maria
AU - Merlini, Luciano
AU - Mora, Marina
AU - Bernasconi, Pia
AU - Gibertini, Sara
AU - Sansone, Valeria
AU - Mongini, Tiziana
AU - Berardinelli, Angela
AU - Pini, Antonella
AU - Liguori, Rocco
AU - Filosto, Massimiliano
AU - Messina, Sonia
AU - Vita, Gianluca
AU - Toscano, Antonio
AU - Vita, Giuseppe
AU - Pane, Marika
AU - Servidei, Serenella
AU - Pegoraro, Elena
AU - Bello, Luca
AU - Travaglini, Lorena
AU - Bertini, Enrico
AU - D'Amico, Adele
AU - Ergoli, Manuela
AU - Politano, Luisa
AU - Torella, Annalaura
AU - Nigro, Vincenzo
AU - Mercuri, Eugenio
AU - Ferlini, Alessandra
N1 - Copyright © 2020 Neri, Rossi, Trabanelli, Mauro, Selvatici, Falzarano, Spedicato, Margutti, Rimessi, Fortunato, Fabris, Gualandi, Comi, Tedeschi, Seia, Fiorillo, Traverso, Bruno, Giardina, Piemontese, Merla, Cau, Marica, Scuderi, Borgione, Tessa, Astrea, Santorelli, Merlini, Mora, Bernasconi, Gibertini, Sansone, Mongini, Berardinelli, Pini, Liguori, Filosto, Messina, Vita, Toscano, Vita, Pane, Servidei, Pegoraro, Bello, Travaglini, Bertini, D'Amico, Ergoli, Politano, Torella, Nigro, Mercuri and Ferlini.
PY - 2020
Y1 - 2020
N2 - Dystrophinopathies are inherited diseases caused by mutations in the dystrophin (DMD) gene for which testing is mandatory for genetic diagnosis, reproductive choices and eligibility for personalized trials. We genotyped the DMD gene in our Italian cohort of 1902 patients (BMD n = 740, 39%; DMD n =1162, 61%) within a nationwide study involving 11 diagnostic centers in a 10-year window (2008-2017). In DMD patients, we found deletions in 57%, duplications in 11% and small mutations in 32%. In BMD, we found deletions in 78%, duplications in 9% and small mutations in 13%. In BMD, there are a higher number of deletions, and small mutations are more frequent than duplications. Among small mutations that are generally frequent in both phenotypes, 44% of DMD and 36% of BMD are nonsense, thus, eligible for stop codon read-through therapy; 63% of all out-of-frame deletions are eligible for single exon skipping. Patients were also assigned to Italian regions and showed interesting regional differences in mutation distribution. The full genetic characterization in this large, nationwide cohort has allowed us to draw several correlations between DMD/BMD genotype landscapes and mutation frequency, mutation types, mutation locations along the gene, exon/intron architecture, and relevant protein domain, with effects on population genetic characteristics and new personalized therapies.
AB - Dystrophinopathies are inherited diseases caused by mutations in the dystrophin (DMD) gene for which testing is mandatory for genetic diagnosis, reproductive choices and eligibility for personalized trials. We genotyped the DMD gene in our Italian cohort of 1902 patients (BMD n = 740, 39%; DMD n =1162, 61%) within a nationwide study involving 11 diagnostic centers in a 10-year window (2008-2017). In DMD patients, we found deletions in 57%, duplications in 11% and small mutations in 32%. In BMD, we found deletions in 78%, duplications in 9% and small mutations in 13%. In BMD, there are a higher number of deletions, and small mutations are more frequent than duplications. Among small mutations that are generally frequent in both phenotypes, 44% of DMD and 36% of BMD are nonsense, thus, eligible for stop codon read-through therapy; 63% of all out-of-frame deletions are eligible for single exon skipping. Patients were also assigned to Italian regions and showed interesting regional differences in mutation distribution. The full genetic characterization in this large, nationwide cohort has allowed us to draw several correlations between DMD/BMD genotype landscapes and mutation frequency, mutation types, mutation locations along the gene, exon/intron architecture, and relevant protein domain, with effects on population genetic characteristics and new personalized therapies.
U2 - 10.3389/fgene.2020.00131
DO - 10.3389/fgene.2020.00131
M3 - Article
C2 - 32194622
VL - 11
SP - 131
JO - Frontiers in Genetics
JF - Frontiers in Genetics
SN - 1664-8021
ER -