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The Genetic Landscape of Dystrophin Mutations in Italy: A Nationwide Study

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 =11...

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Autores principales: Neri, Marcella, Rossi, Rachele, Trabanelli, Cecilia, Mauro, Antonio, Selvatici, Rita, Falzarano, Maria Sofia, Spedicato, Noemi, Margutti, Alice, Rimessi, Paola, Fortunato, Fernanda, Fabris, Marina, Gualandi, Francesca, Comi, Giacomo, Tedeschi, Silvana, Seia, Manuela, Fiorillo, Chiara, Traverso, Monica, Bruno, Claudio, Giardina, Emiliano, Piemontese, Maria Rosaria, Merla, Giuseppe, Cau, Milena, Marica, Monica, Scuderi, Carmela, Borgione, Eugenia, Tessa, Alessandra, Astrea, Guia, Santorelli, Filippo Maria, Merlini, Luciano, Mora, Marina, Bernasconi, Pia, Gibertini, Sara, Sansone, Valeria, Mongini, Tiziana, Berardinelli, Angela, Pini, Antonella, Liguori, Rocco, Filosto, Massimiliano, Messina, Sonia, Vita, Gianluca, Toscano, Antonio, Vita, Giuseppe, Pane, Marika, Servidei, Serenella, Pegoraro, Elena, Bello, Luca, Travaglini, Lorena, Bertini, Enrico, D'Amico, Adele, Ergoli, Manuela, Politano, Luisa, Torella, Annalaura, Nigro, Vincenzo, Mercuri, Eugenio, Ferlini, Alessandra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063120/
https://www.ncbi.nlm.nih.gov/pubmed/32194622
http://dx.doi.org/10.3389/fgene.2020.00131
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author Neri, Marcella
Rossi, Rachele
Trabanelli, Cecilia
Mauro, Antonio
Selvatici, Rita
Falzarano, Maria Sofia
Spedicato, Noemi
Margutti, Alice
Rimessi, Paola
Fortunato, Fernanda
Fabris, Marina
Gualandi, Francesca
Comi, Giacomo
Tedeschi, Silvana
Seia, Manuela
Fiorillo, Chiara
Traverso, Monica
Bruno, Claudio
Giardina, Emiliano
Piemontese, Maria Rosaria
Merla, Giuseppe
Cau, Milena
Marica, Monica
Scuderi, Carmela
Borgione, Eugenia
Tessa, Alessandra
Astrea, Guia
Santorelli, Filippo Maria
Merlini, Luciano
Mora, Marina
Bernasconi, Pia
Gibertini, Sara
Sansone, Valeria
Mongini, Tiziana
Berardinelli, Angela
Pini, Antonella
Liguori, Rocco
Filosto, Massimiliano
Messina, Sonia
Vita, Gianluca
Toscano, Antonio
Vita, Giuseppe
Pane, Marika
Servidei, Serenella
Pegoraro, Elena
Bello, Luca
Travaglini, Lorena
Bertini, Enrico
D'Amico, Adele
Ergoli, Manuela
Politano, Luisa
Torella, Annalaura
Nigro, Vincenzo
Mercuri, Eugenio
Ferlini, Alessandra
author_facet Neri, Marcella
Rossi, Rachele
Trabanelli, Cecilia
Mauro, Antonio
Selvatici, Rita
Falzarano, Maria Sofia
Spedicato, Noemi
Margutti, Alice
Rimessi, Paola
Fortunato, Fernanda
Fabris, Marina
Gualandi, Francesca
Comi, Giacomo
Tedeschi, Silvana
Seia, Manuela
Fiorillo, Chiara
Traverso, Monica
Bruno, Claudio
Giardina, Emiliano
Piemontese, Maria Rosaria
Merla, Giuseppe
Cau, Milena
Marica, Monica
Scuderi, Carmela
Borgione, Eugenia
Tessa, Alessandra
Astrea, Guia
Santorelli, Filippo Maria
Merlini, Luciano
Mora, Marina
Bernasconi, Pia
Gibertini, Sara
Sansone, Valeria
Mongini, Tiziana
Berardinelli, Angela
Pini, Antonella
Liguori, Rocco
Filosto, Massimiliano
Messina, Sonia
Vita, Gianluca
Toscano, Antonio
Vita, Giuseppe
Pane, Marika
Servidei, Serenella
Pegoraro, Elena
Bello, Luca
Travaglini, Lorena
Bertini, Enrico
D'Amico, Adele
Ergoli, Manuela
Politano, Luisa
Torella, Annalaura
Nigro, Vincenzo
Mercuri, Eugenio
Ferlini, Alessandra
author_sort Neri, Marcella
collection PubMed
description 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.
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spelling pubmed-70631202020-03-19 The Genetic Landscape of Dystrophin Mutations in Italy: A Nationwide Study Neri, Marcella Rossi, Rachele Trabanelli, Cecilia Mauro, Antonio Selvatici, Rita Falzarano, Maria Sofia Spedicato, Noemi Margutti, Alice Rimessi, Paola Fortunato, Fernanda Fabris, Marina Gualandi, Francesca Comi, Giacomo Tedeschi, Silvana Seia, Manuela Fiorillo, Chiara Traverso, Monica Bruno, Claudio Giardina, Emiliano Piemontese, Maria Rosaria Merla, Giuseppe Cau, Milena Marica, Monica Scuderi, Carmela Borgione, Eugenia Tessa, Alessandra Astrea, Guia Santorelli, Filippo Maria Merlini, Luciano Mora, Marina Bernasconi, Pia Gibertini, Sara Sansone, Valeria Mongini, Tiziana Berardinelli, Angela Pini, Antonella Liguori, Rocco Filosto, Massimiliano Messina, Sonia Vita, Gianluca Toscano, Antonio Vita, Giuseppe Pane, Marika Servidei, Serenella Pegoraro, Elena Bello, Luca Travaglini, Lorena Bertini, Enrico D'Amico, Adele Ergoli, Manuela Politano, Luisa Torella, Annalaura Nigro, Vincenzo Mercuri, Eugenio Ferlini, Alessandra Front Genet Genetics 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. Frontiers Media S.A. 2020-03-03 /pmc/articles/PMC7063120/ /pubmed/32194622 http://dx.doi.org/10.3389/fgene.2020.00131 Text en 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 http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Neri, Marcella
Rossi, Rachele
Trabanelli, Cecilia
Mauro, Antonio
Selvatici, Rita
Falzarano, Maria Sofia
Spedicato, Noemi
Margutti, Alice
Rimessi, Paola
Fortunato, Fernanda
Fabris, Marina
Gualandi, Francesca
Comi, Giacomo
Tedeschi, Silvana
Seia, Manuela
Fiorillo, Chiara
Traverso, Monica
Bruno, Claudio
Giardina, Emiliano
Piemontese, Maria Rosaria
Merla, Giuseppe
Cau, Milena
Marica, Monica
Scuderi, Carmela
Borgione, Eugenia
Tessa, Alessandra
Astrea, Guia
Santorelli, Filippo Maria
Merlini, Luciano
Mora, Marina
Bernasconi, Pia
Gibertini, Sara
Sansone, Valeria
Mongini, Tiziana
Berardinelli, Angela
Pini, Antonella
Liguori, Rocco
Filosto, Massimiliano
Messina, Sonia
Vita, Gianluca
Toscano, Antonio
Vita, Giuseppe
Pane, Marika
Servidei, Serenella
Pegoraro, Elena
Bello, Luca
Travaglini, Lorena
Bertini, Enrico
D'Amico, Adele
Ergoli, Manuela
Politano, Luisa
Torella, Annalaura
Nigro, Vincenzo
Mercuri, Eugenio
Ferlini, Alessandra
The Genetic Landscape of Dystrophin Mutations in Italy: A Nationwide Study
title The Genetic Landscape of Dystrophin Mutations in Italy: A Nationwide Study
title_full The Genetic Landscape of Dystrophin Mutations in Italy: A Nationwide Study
title_fullStr The Genetic Landscape of Dystrophin Mutations in Italy: A Nationwide Study
title_full_unstemmed The Genetic Landscape of Dystrophin Mutations in Italy: A Nationwide Study
title_short The Genetic Landscape of Dystrophin Mutations in Italy: A Nationwide Study
title_sort genetic landscape of dystrophin mutations in italy: a nationwide study
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063120/
https://www.ncbi.nlm.nih.gov/pubmed/32194622
http://dx.doi.org/10.3389/fgene.2020.00131
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