The nonsense mutation stop+4 model correlates with motor changes in Duchenne muscular dystrophy期刊界 All Journals 搜尽天下杂志传播学术成果专业期刊搜索期刊信息化学术搜索

The nonsense mutation stop+4 model correlates with motor changes in Duchenne muscular dystrophy

Authors:	Claudia Brogna Giorgia Coratti Rachele Rossi Marcella Neri Sonia Messina Adele D’ Amico Claudio Bruno Simona Lucibello Gianluca Vita Angela Berardinelli Francesca Magri Federica Ricci Marina Pedemonte Tiziana Mongini Roberta Battini Luca Bello Elena Pegoraro Giovanni Baranello Eugenio Mercuri

Affiliation:	1. Pediatric Neurology, Università Cattolica del Sacro Cuore, Rome, Italy;2. Centro Clinico Nemo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo Agostino Gemelli 8, Rome 00152, Italy;3. Unit of Medical Genetics, Department of Medical Sciences, University of Ferrara, Ferrara, Italy;4. Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy;5. Nemo SUD Clinical Center, University Hospital “G. Martino”, Messina, Italy;6. Department of Neurosciences, Unit of Neuromuscular and Neurodegenerative Disorders, Bambino Gesù Children''s Hospital, IRCCS, Rome, Italy;7. Center of Translational and Experimental Myology, IRCCS Istituto Giannina Gaslini, Genoa, Italy;8. Child Neurology and Psychiatry Unit, ‘‘Casimiro Mondino’’ Foundation, Pavia, Italy;9. Department of Pathophysiology and Transplantation, Fondazione IRCCS Ca’ Grande Ospedale Maggiore Policlinico, Dino Ferrari Center, , University of Milan, Milan, Italy;12. Neuromuscular Center, AOU Città della Salute e della Scienza, University of Torino, Italy;13. Department of Developmental Neuroscience, Stella Maris Institute, Pisa, Italy;14. Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy;15. Department of Neurosciences, University of Padua, Padua, Italy;p. Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy;q. Cardiomiologia e Genetica Medica, Dipartimento di Medicina Sperimentale, Università della Campania Luigi Vanvitelli, Napoli, Italy;r. The NEMO Center in Milan, Neurorehabilitation Unit, University of Milan, ASST Niguarda Hospital, Milan, Italy;s. Metabolic Unit, A. Meyer Children''s Hospital, Florence, Italy;t. Department of Child Neurology, University Hospitals Leuven, Leuven, Belgium;u. Neuromuscular Repair Unit, Inspe and Division of Neuroscience, IRCSS San Raffaele Scientific Institute, Milan, Italy;v. Department of Health Sciences (DISSAL), University of Genova, Genoa, Italy;1. Department of Neurology, Kansai Medical University, 2-5-1, Shinmachi, Hirakata, Osaka 5731010, Japan;2. Department of Microbiology, Kansai Medical University, 2-5-1, Shinmachi, Hirakata, Osaka 5731010, Japan;1. UOC Neurofisiopatologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Agostino Gemelli 8, Rome 00168, Italy;2. Department of Neurosciences, Unit of Neuromuscular and Neurodegenerative Disorders, Laboratory of Molecular Medicine, Bambino Gesù Children''s Research Hospital, IRCCS, Rome, Italy;3. Dipartimento Universitario di Neuroscienze, Università Cattolica del Sacro Cuore, Rome, Italy;4. Fondazione UILDM LAZIO onlus, Italy;1. Department of Medical Genetics, Capital Institute of Pediatrics, Beijing, China;2. Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China;3. Department of Neurology, Children''s Hospital Affiliated Capital Institute of Pediatrics, Beijing, China

Abstract:	The aim was to assess 3-year longitudinal data using 6MWT in 26 ambulant boys affected by DMD carrying nonsense mutations and to compare their results to other small mutations. We also wished to establish, within the nonsense mutations group, patterns of change according to several variables. Patients with nonsense mutations were categorized according to the stop codon type newly created by the mutation and also including the adjacent 5′ (upstream) and 3′ (downstream) nucleotides. No significant difference was found between nonsense mutations and other small mutations (p > 0.05) on the 6MWT. Within the nonsense mutations group, there was no difference in 6MWT when the patients were subdivided according to: Type of stop codon, frame status of exons involved, protein domain affected. In contrast, there was a difference when the stop codon together with the 3′ adjacent nucleotide (“stop+4 model”) was considered (p < 0.05) with patients with stop codon TGA and 3′ adjacent nucleotide G (TGAG) having a more rapid decline. Our finding suggest that the stop+4 model may help in predicting functional changes. This data will be useful at the time of interpreting the long term follow up of patients treated with Ataluren that are becoming increasingly available.

Keywords:
本文献已被 ScienceDirect 等数据库收录！

设为首页 | 免责声明 | 关于勤云 | 加入收藏