المؤلفون: Theodora Markati, Maryam Oskoui, Michelle A Farrar, Tina Duong, Nathalie Goemans, Laurent Servais

المصدر: The Lancet Neurology. 21:814-829

مصطلحات موضوعية: Dystrophin, Muscular Dystrophy, Duchenne, Genotype, Humans, Exons, Genetic Therapy, Neurology (clinical)

الوصف: Duchenne muscular dystrophy is an X-linked disease caused by the absence of functional dystrophin in the muscle cells. Major advances have led to the development of gene therapies, tools that induce exon skipping, and other therapeutic approaches, including treatments targeting molecular pathways downstream of the absence of functional dystrophin. However, glucocorticoids remain the only treatment unequivocally shown to slow disease progression, despite the adverse effects associated with their long-term use. Besides glucocorticoids, which are standard care, five compounds have received regulatory approval in some but not all jurisdictions, with further efficacy results being awaited. Several compounds with promising results in early-phase clinical trials have not met their efficacy endpoints in late-phase trials, but the clinical development of many other compounds is ongoing. The current landscape is complicated by the number of compounds in various stages of development, their various mechanisms of action, and their genotype-specific applicability. The difficulties of clinical development that arise from both the rarity and variability of Duchenne muscular dystrophy might be overcome in the future by use of sensitive biomarkers, natural history data, and ameliorated trial designs.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::820ad3542d282c18a7729900e4d102abTest
https://doi.org/10.1016/s1474-4422Test(22)00125-9

المؤلفون: Linda Lowes, Navid Khan, Lindsay N. Alfano, Helen Eliopoulos, Nathalie Goemans, Eugenio Mercuri, Craig M. McDonald, Jerry R. Mendell, Nanshi Sha

المصدر: Journal of Neuromuscular Diseases

مصطلحات موضوعية: Research Report, Duchenne muscular dystrophy, Male, medicine.medical_specialty, BOYS, Neuromuscular disease, Adolescent, Clinical Neurology, Walk Test, Walking, Eteplirsen, dystrophin, Morpholinos, Internal medicine, loss of ambulation, END-POINTS, medicine, Humans, In patient, eteplirsen, Child, POPULATION, Retrospective Studies, Science & Technology, 6-minute walk test, biology, business.industry, Neurosciences, Exons, medicine.disease, Duchenne, Exon skipping, PREVALENCE, Natural history, Muscular Dystrophy, Duchenne, Neurology, Case-Control Studies, Ambulatory, Mutation, biology.protein, Neurology (clinical), Neurosciences & Neurology, MUSCLE DISEASE, Dystrophin, business, Life Sciences & Biomedicine, EXONDYS 51

الوصف: BACKGROUND: Duchenne muscular dystrophy (DMD) is a rare, X-linked, fatal, degenerative neuromuscular disease caused by DMD gene mutations. A relationship between exon skipping and dystrophin production in exon 51-amenable patients treated with eteplirsen (EXONDYS 51®) is established. Once-weekly eteplirsen significantly increased dystrophin, with slower decline in ambulatory function compared to baseline. Long-term treatment with eteplirsen leads to accumulation of dystrophin over time and observed functional benefits in patients with DMD. OBJECTIVE: Compare long-term ambulatory function in eteplirsen-treated patients versus controls. METHODS: Study 201/202 included 12 eteplirsen-treated patients assessed twice/year for ambulatory function over 4 years. Ambulatory evaluations (6-minute walk test [6MWT], loss of ambulation, and North Star Ambulatory Assessment [NSAA]) were compared with matched controls from Italian Telethon and Leuven registries. RESULTS: At Years 3 and 4, eteplirsen-treated patients demonstrated markedly greater mean 6MWT than controls (difference in change from baseline of 132 m [95%CI (29, 235), p = 0.015] at Year 3 and 159 m [95%CI (66, 253), p = 0.002] at Year 4). At Year 4, a significantly greater proportion of eteplirsen-treated patients were still ambulant versus controls (10/12 vs 3/11; p = 0.020). At Year 3, eteplirsen-treated patients demonstrated milder NSAA decline versus controls (difference in change from baseline of 2.6, 95%CI [-6, 11]), however, the difference was not statistically significant; Year 4 control NSAA data were not available. CONCLUSION: In this retrospective matched control study, eteplirsen treatment resulted in attenuation of ambulatory decline over a 4-year observation period, supporting long-term benefit in patients with DMD. ispartof: JOURNAL OF NEUROMUSCULAR DISEASES vol:8 issue:4 pages:469-479 ispartof: location:Netherlands status: published

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http://europepmc.org/articles/PMC8385516Test

المؤلفون: Robin Duelen, Domiziana Costamagna, Guillaume Gilbert, Liesbeth De Waele, Nathalie Goemans, Kaat Desloovere, Catherine M. Verfaillie, Karin R. Sipido, Gunnar M. Buyse, Maurilio Sampaolesi

مصطلحات موضوعية: musculoskeletal diseases, Duchenne muscular dystrophy, muscular dystrophy, induced pluripotent stem cells, cardiac, adenosine triphosphate, Biochemistry, cell survival, dystrophin, acetylcysteine, Genetics, hiPSC modeling, oxidative stress, Myocytes, Cardiac, CRISPR-cas systems, humans, duchenne muscular dystrophy, reactive oxygen species, gene editing, NADPH oxidase 4, duchenne, oxadiazoles, Cell Biology, myocytes, Muscular Dystrophy, Duchenne, cardiomyopathy, CRISPR-Cas9, NADPH oxidase NOX4, cell differentiation, mitochondria, Developmental Biology

الوصف: Duchenne muscular dystrophy (DMD) is a progressive muscle disorder caused by mutations in the Dystrophin gene. Cardiomyopathy is a major cause of early death. We used DMD-patient-specific human induced pluripotent stem cells (hiPSCs) to model cardiomyopathic features and unravel novel pathologic insights. Cardiomyocytes (CMs) differentiated from DMD hiPSCs showed enhanced premature cell death due to significantly elevated intracellular reactive oxygen species (ROS) resulting from depolarized mitochondria and increased NADPH oxidase 4 (NOX4). CRISPR-Cas9 correction of Dystrophin restored normal ROS levels. ROS reduction by N-acetyl-L-cysteine (NAC), ataluren (PTC124), and idebenone improved hiPSC-CM survival. We show that oxidative stress in DMD hiPSC-CMs was counteracted by stimulating adenosine triphosphate (ATP) production. ATP can bind to NOX4 and partially inhibit the ROS production. Considering the complexity and the early cellular stress responses in DMD cardiomyopathy, we propose targeting ROS production and preventing detrimental effects of NOX4 on DMD CMs as promising therapeutic strategy. ispartof: STEM CELL REPORTS vol:17 issue:2 pages:352-368 ispartof: location:United States status: published

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http://hdl.handle.net/11573/1625497Test

المؤلفون: L. De Waele, Gunnar M. Buyse, Karin R. Sipido, Nathalie Goemans, Catherine M. Verfaillie, Kaat Desloovere, Guillaume Gilbert, Maurilio Sampaolesi, Domiziana Costamagna, Robin Duelen

مصطلحات موضوعية: musculoskeletal diseases, NADPH oxidase, biology, Duchenne muscular dystrophy, NOX4, Muscle disorder, Mitochondrion, medicine.disease, Cell biology, Ataluren, chemistry.chemical_compound, chemistry, medicine, biology.protein, Idebenone, Dystrophin, medicine.drug

الوصف: Duchenne muscular dystrophy (DMD) is an X-linked progressive muscle disorder, caused by mutations in the Dystrophin gene. Cardiomyopathy is one of the major causes of early death. In this study, we used DMD patient-specific induced pluripotent stem cells (iPSCs) to model cardiomyopathic features in DMD and unravel novel pathological mechanistic insights. Cardiomyocytes (CMs) differentiated from DMD iPSCs showed enhanced premature cell death, due to significantly elevated intracellular reactive oxygen species (ROS) concentrations, as a result of depolarized mitochondria and high NADPH oxidase 4 (NOX4) protein levels. Genetic correction of Dystrophin through CRISPR/Cas9 editing restored normal ROS levels. Application of ROS reduction by N-acetyl-L-cysteine (NAC), partial Dystrophin re-expression by ataluren (PTC124) and enhancing mitochondrial electron transport chain function by idebenone improved cell survival of DMD iPSC-CMs. We show applications that could counteract the detrimental oxidative stress environment in DMD iPSC-CMs by stimulating adenosine triphosphate (ATP) production. ATP could bind to the ATP-binding domain in the NOX4 enzyme, and we demonstrate that ATP resulted in partial inhibition of the NADPH-dependent ROS production of NOX4.Considering the complexity and the early cellular stress responses in DMD cardiomyopathy, we propose to target ROS production and prevent the detrimental effects of NOX4 on DMD CMs as a promising therapeutic strategy.GRAPHICAL ABSTRACTThe use of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) from Duchenne muscular dystrophy (DMD) patients to model cardiomyopathic features in DMD and unravel novel pathological mechanistic insights.DMD iPSC-CMs showed accelerated cell death, caused by increased intracellular reactive oxygen species (ROS) levels. By intervention at different target sites, beneficial effects on the mitochondrial membrane potential (ΔΨm) and the expression and ROS-producing activity of the cardiac-specific NADPH-oxidase 4 isoform (NOX4) were observed, resulting in an increased cell survival and function of DMD iPSC-CMs.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::afd0f29c5d13dbbaccbbc615b74b7216Test
https://doi.org/10.1101/2021.09.13.460090Test

المؤلفون: Barry J. Byrne, Olga Mitelman, Sourav Santra, Jerry R. Mendell, Ashish Dugar, Anne M. Connolly, Hoda Z. Abdel-Hamid, Nathalie Goemans, Eugenio Mercuri, Peter Heydemann, Kathryn R. Wagner, Craig M. McDonald, Crystal Proud, Perry B. Shieh, James Signorovitch

المصدر: Journal of neuromuscular diseases. 9(1)

مصطلحات موضوعية: Duchenne muscular dystrophy, Male, Vital capacity, medicine.medical_specialty, Time Factors, 6-minutewalk test, Adolescent, Vital Capacity, Clinical Neurology, Walk Test, Eteplirsen, dystrophin, Pulmonary function testing, Morpholinos, DUCHENNE MUSCULAR-DYSTROPHY, 6-MINUTE WALK TEST, FEV1/FVC ratio, DRISAPERSEN, forced vital capacity, loss of ambulation, Internal medicine, END-POINTS, Outcome Assessment, Health Care, Medicine, Humans, eteplirsen, Prospective Studies, Registries, Mobility Limitation, Child, Retrospective Studies, Science & Technology, business.industry, Proportional hazards model, DISEASE PROGRESSION, Neurosciences, Repeated measures design, NATURAL-HISTORY, Muscular Dystrophy, Duchenne, Neurology, Ambulatory, Disease Progression, TRIAL, Neurosciences & Neurology, Neurology (clinical), business, Life Sciences & Biomedicine, Natural history study

الوصف: BACKGROUND: Studies 4658-201/202 (201/202) evaluated treatment effects of eteplirsen over 4 years in patients with Duchenne muscular dystrophy and confirmed exon-51 amenable genetic mutations. Chart review Study 4658-405 (405) further followed these patients while receiving eteplirsen during usual clinical care. OBJECTIVE: To compare long-term clinical outcomes of eteplirsen-treated patients from Studies 201/202/405 with those of external controls. METHODS: Median total follow-up time was approximately 6 years of eteplirsen treatment. Outcomes included loss of ambulation (LOA) and percent-predicted forced vital capacity (FVC%p). Time to LOA was compared between eteplirsen-treated patients and standard of care (SOC) external controls and was measured from eteplirsen initiation in 201/202 or, in the SOC group, from the first study visit. Comparisons were conducted using univariate Kaplan-Meier analyses and log-rank tests, and multivariate Cox proportional hazards models with regression adjustment for baseline characteristics. Annual change in FVC%p was compared between eteplirsen-treated patients and natural history study patients using linear mixed models with repeated measures. RESULTS: Data were included from all 12 patients in Studies 201/202 and the 10 patients with available data from 405. Median age at LOA was 15.16 years. Eteplirsen-treated patients experienced a statistically significant longer median time to LOA by 2.09 years (5.09 vs. 3.00 years, p

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https://pubmed.ncbi.nlm.nih.gov/34420980Test

المؤلفون: Sonia Messina, Claudio Bruno, E. Mazzone, Eugenio Mercuri, Valeria A. Sansone, Claudia Brogna, Gianluca Vita, Francesco Muntoni, Marika Pane, Tiziana Mongini, Giovanni Baranello, Erik H. Niks, Mary Chesshyre, Francesca Magri, Volker Straub, Enrico Bertini, Elena Pegoraro, Luca Bello, Alice Donati, Silvana De Lucia, Stefano C. Previtali, Valeria Ricotti, Adele D'Amico, Jean-Yves Hogrel, Nathalie Goemans, Roberta Battini, Giacomo P. Comi, Laurent Servais, Giorgia Coratti, Federica Ricci, Imelda J. M. de Groot, Luisa Politano, Angela Berardinelli

المصدر: PLoS ONE, 16(6). PUBLIC LIBRARY SCIENCE
PLoS ONE
PLoS ONE, Vol 16, Iss 6, p e0253882 (2021)

مصطلحات موضوعية: Male, Heredity, Genetic Linkage, Epidemiology, Physiology, Duchenne muscular dystrophy, Walking, Duchenne Muscular Dystrophy, Severity of Illness Index, Muscular Dystrophies, Dystrophin, Exon, 0302 clinical medicine, Medical Conditions, Medicine and Health Sciences, 030212 general & internal medicine, Muscular Dystrophy, Longitudinal Studies, Child, Baseline values, Multidisciplinary, Settore MED/48 - SCIENZE INFERMIERISTICHE E TECNICHE NEURO-PSICHIATRICHE E RIABILITATIVE, Organic Compounds, Men, Exons, Multidisciplinary Sciences, Chemistry, Deletion Mutation, Neurology, X-Linked Traits, Sex Linkage, Ambulatory, Physical Sciences, Disease Progression, Medicine, Science & Technology - Other Topics, Steroids, exon skipping, Research Article, medicine.medical_specialty, Science, Natural history of disease, 03 medical and health sciences, Settore MED/39 - NEUROPSICHIATRIA INFANTILE, Internal medicine, medicine, Genetics, Humans, Clinical Genetics, Science & Technology, business.industry, Biological Locomotion, Organic Chemistry, Chemical Compounds, Biology and Life Sciences, Human Genetics, medicine.disease, Duchenne, Human genetics, Exon skipping, Follow-Up Studies, Muscular Dystrophy, Duchenne, Mutation, Clinical trial, Natural History of Disease, Medical Risk Factors, business, 030217 neurology & neurosurgery

الوصف: Introduction The aim of this study was to report 36-month longitudinal changes using the North Star Ambulatory Assessment (NSAA) in ambulant patients affected by Duchenne muscular dystrophy amenable to skip exons 44, 45, 51 or 53. Materials and methods We included 101 patients, 34 had deletions amenable to skip exon 44, 25 exon 45, 19 exon 51, and 28 exon 53, not recruited in any ongoing clinical trials. Five patients were counted to skip exon 51 and 53 since they had a single deletion of exon 52. Results The difference between subgroups (skip 44, 45, 51 and 53) was significant at 12 (p = 0.043), 24 (p = 0.005) and 36 months (p≤0.001). Discussion Mutations amenable to skip exons 53 and 51 had lower baseline values and more negative changes than the other subgroups while those amenable to skip exon 44 had higher scores both at baseline and at follow up. Conclusion Our results confirm different progression of disease in subgroups of patients with deletions amenable to skip different exons. This information is relevant as current long term clinical trials are using the NSAA in these subgroups of mutations.

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http://hdl.handle.net/1887/3249481Test

المؤلفون: Shin'ichi Takeda, Annemieke Aartsma-Rus, Eugenio Mercuri, Nathalie Goemans, Dongsheng Duan

المصدر: Nature Reviews Disease Primers, 7(1). NATURE RESEARCH

مصطلحات موضوعية: musculoskeletal diseases, biology, business.industry, Duchenne muscular dystrophy, Cardiomyopathy, General Medicine, Disease, Assisted ventilation, Bioinformatics, medicine.disease, Dystrophin, Muscular Dystrophy, Duchenne, Premature death, Disease Models, Animal, biology.protein, medicine, Animals, Humans, Muscular dystrophy, business, Genetic diagnosis

الوصف: Duchenne muscular dystrophy is a severe, progressive, muscle-wasting disease that leads to difficulties with movement and, eventually, to the need for assisted ventilation and premature death. The disease is caused by mutations in DMD (encoding dystrophin) that abolish the production of dystrophin in muscle. Muscles without dystrophin are more sensitive to damage, resulting in progressive loss of muscle tissue and function, in addition to cardiomyopathy. Recent studies have greatly deepened our understanding of the primary and secondary pathogenetic mechanisms. Guidelines for the multidisciplinary care for Duchenne muscular dystrophy that address obtaining a genetic diagnosis and managing the various aspects of the disease have been established. In addition, a number of therapies that aim to restore the missing dystrophin protein or address secondary pathology have received regulatory approval and many others are in clinical development.Duchenne muscular dystrophy is an X-linked progressive, muscle-wasting disease that manifests in childhood as difficulties with movement. This Primer by Aartsma-Rus and colleagues discusses the clinical presentation, epidemiology, pathophysiology, genetic diagnosis and treatment of this disorder.

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https://pubmed.ncbi.nlm.nih.gov/33602943Test

المؤلفون: Craig M. McDonald, Kathryn R. Wagner, Erica Koenig, Jyoti Malhotra, Navid Khan, Perry B. Shieh, Promovi Trial Clinical Investigators, Baoguang Han, Hoda Z. Abdel-Hamid, Anne M. Connolly, Nathalie Goemans, Wenfei Zhang, Emma Ciafaloni, Eugenio Mercuri, Jerry R. Mendell

المصدر: Journal of Neuromuscular Diseases

مصطلحات موضوعية: Male, Research Report, 0301 basic medicine, safety, medicine.medical_specialty, Adolescent, Duchenne muscular dystrophy, Vital Capacity, Clinical Neurology, Eteplirsen, Morpholinos, Dystrophin, 03 medical and health sciences, 0302 clinical medicine, treatment efficacy, Internal medicine, medicine, Humans, Muscular dystrophy, Child, Adverse effect, Science & Technology, biology, business.industry, duchenne, Neurosciences, clinical trial, Exons, medicine.disease, Duchenne, Exon skipping, Muscular Dystrophy, Duchenne, Clinical trial, AMBULATION, 030104 developmental biology, Neurology, phase 3, Mutation, Cohort, Disease Progression, biology.protein, Neurology (clinical), Neurosciences & Neurology, business, Life Sciences & Biomedicine, 030217 neurology & neurosurgery

الوصف: BackgroundEteplirsen received accelerated FDA approval for treatment of Duchenne muscular dystrophy (DMD) with mutations amenable to exon 51 skipping, based on demonstrated dystrophin production.ObjectiveTo report results from PROMOVI, a phase 3, multicenter, open-label study evaluating efficacy and safety of eteplirsen in a larger cohort.MethodsAmbulatory patients aged 7-16 years, with confirmed mutations amenable to exon 51 skipping, received eteplirsen 30 mg/kg/week intravenously for 96 weeks. An untreated cohort with DMD not amenable to exon 51 skipping was also enrolled.Results78/79 eteplirsen-treated patients completed 96 weeks of treatment. 15/30 untreated patients completed the study; this cohort was considered an inappropriate control group because of genotype-driven differences in clinical trajectory. At Week 96, eteplirsen-treated patients showed increased exon skipping (18.7-fold) and dystrophin protein (7-fold) versus baseline. Post-hoc comparisons with patients from eteplirsen phase 2 studies (4658-201/202) and mutation-matched external natural history controls confirmed previous results, suggesting clinically notable attenuation of decline on the 6-minute walk test over 96 weeks (PROMOVI: -68.9 m; phase 2 studies: -67.3 m; external controls: -133.8 m) and significant attenuation of percent predicted forced vital capacity annual decline (PROMOVI: -3.3%, phase 2 studies: -2.2%, external controls: -6.0%; p

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https://lirias.kuleuven.be/handle/20.500.12942/706497Test

المؤلفون: Stefano C. Previtali, Federica Ricci, Marika Pane, Angela Berardinelli, Valeria A. Sansone, Tiziana Mongini, Claudia Brogna, Gianluca Vita, Marina Pedemonte, Eugenio Mercuri, Luisa Politano, Francesca Magri, Giorgia Coratti, Roberta Battini, Rachele Rossi, Claudio Bruno, Sonia Messina, Giacomo P. Comi, Giovanni Baranello, Elena Pegoraro, Francesca Bovis, Nathalie Goemans, Adele D’ Amico, Alessandra Ferlini, Alice Donati, Enrico Bertini, Luca Bello, Simona Lucibello, Emilio Albamonte, Marcella Neri

مصطلحات موضوعية: 0301 basic medicine, Male, Duchenne muscular dystrophy, medicine.disease_cause, Settore MED/03 - GENETICA MEDICA, Dystrophin, chemistry.chemical_compound, Exon, 0302 clinical medicine, Belgium, Missense mutation, Longitudinal Studies, Muscular Dystrophy, Child, Genetics (clinical), Genetics, Mutation, Oxadiazoles, Nonsense mutation, Settore MED/48 - SCIENZE INFERMIERISTICHE E TECNICHE NEURO-PSICHIATRICHE E RIABILITATIVE, Exons, Stop codon, Settore MED/26 - NEUROLOGIA, Neurology, Italy, Codon, Nonsense, Child, Preschool, Settore BIO/18 - GENETICA, Walk Test, Frameshift mutation, 03 medical and health sciences, Settore MED/39 - NEUROPSICHIATRIA INFANTILE, medicine, Humans, Preschool, Codon, business.industry, Duchenne, Stop+4 model, medicine.disease, Ataluren, Muscular Dystrophy, Duchenne, 030104 developmental biology, chemistry, Nonsense, Pediatrics, Perinatology and Child Health, Neurology (clinical), business, 030217 neurology & neurosurgery

الوصف: 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.

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http://hdl.handle.net/10807/182743Test

المؤلفون: Hilde Van Esch, Luc Dehaspe, Kristl G. Claeys, Joris Vermeesch, Nathalie Goemans, Thomy de Ravel, Kris Van Den Bogaert, Valerie Race, Hilde Peeters, Eric Legius, Jazz Storms, Koenraad Devriendt, Nathalie Brison, Darine Villela, Liesbeth De Waele

المساهمون: Medical Genetics

مصطلحات موضوعية: 0301 basic medicine, Adult, congenital, hereditary, and neonatal diseases and abnormalities, DNA Copy Number Variations, endocrine system diseases, Noninvasive Prenatal Testing, Population, Sequence Analysis, DNA/ethics, 030105 genetics & heredity, DNA Copy Number Variations/genetics, Noninvasive Prenatal Testing/ethics, Dystrophin, 03 medical and health sciences, Prenatal Diagnosis, Prenatal Diagnosis/ethics, mental disorders, medicine, Humans, Copy-number variation, education, Genetics (clinical), Genetics, Dystrophin/genetics, Pregnancy, education.field_of_study, Incidental Findings, business.industry, Sequence Analysis, DNA, medicine.disease, Pathogenicity, fetus, NIPS, 030104 developmental biology, Prenatal screening, Dmd gene, secondary findings, Female, pregnancy, business, DMD gene, maternal CNV

الوصف: PURPOSE: Noninvasive prenatal screening (NIPS) using genome sequencing also reveals maternal copy-number variations (CNVs). Those CNVs can be clinically actionable or harmful to the fetus if inherited. CNVs in the DMD gene potentially causing dystrophinopathies are among the most commonly observed maternal CNVs. We present our experience with maternal DMD gene CNVs detected by NIPS. METHODS: We analyzed the data of maternal CNVs detected in the DMD gene revealed by NIPS. RESULTS: Of 26,123 NIPS analyses, 16 maternal CNVs in the DMD gene were detected (1/1632 pregnant women). Variant classification regarding pathogenicity and phenotypic severity was based on public databases, segregation analysis in the family, and prediction of the effect on the reading frame. Ten CNVs were classified as pathogenic, four as benign, and two remained unclassified. CONCLUSION: NIPS leverages CNV screening in the general population of pregnant women. We implemented a strategy for the interpretation and the return of maternal CNVs in the DMD gene detected by NIPS. ispartof: GENETICS IN MEDICINE vol:21 issue:12 pages:2774-2780 ispartof: location:United States status: published

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https://lirias.kuleuven.be/handle/123456789/638443Test