Variations in Duchenne muscular dystrophy clinical course in a multi-ethnic UK population: Are there potential influencing factors other than genetic modifiers?

2016 ◽  
Vol 26 ◽  
pp. S97
Author(s):  
H. Roper ◽  
M. Hufton
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Influencing Factors ◽  
Clinical Course ◽  
Genetic Modifiers

scholarly journals Genetic modifiers of respiratory function in Duchenne muscular dystrophy

2020 ◽  
Vol 7 (5) ◽  
pp. 786-798
Author(s):  
Luca Bello ◽  
Grazia D’Angelo ◽  
Matteo Villa ◽  
Aurora Fusto ◽  
Sara Vianello ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Respiratory Function ◽  
Genetic Modifiers

scholarly journals Becker muscular dystrophy caused by exon 2-truncating mutation of DMD

2019 ◽  
Vol 6 (1) ◽  
Author(s):  
Tetsuhiko Ikeda ◽  
Hidehiko Fujinaka ◽  
Kiyoe Goto ◽  
Takashi Nakajima ◽  
Tetsuo Ozawa
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Frameshift Mutation ◽  
Clinical Course ◽  
Becker Muscular Dystrophy ◽  
Exon 2 ◽  
Mild Phenotype ◽  
Frameshift Mutations ◽  
Stop Codons ◽  
Truncating Mutation

AbstractNonsense and frameshift mutations of the dystrophin (DMD) gene usually cause severe Duchenne muscular dystrophy (DMD). Interestingly, however, premature stop codons in exons 1 and 2 result in relatively mild Becker muscular dystrophy (BMD). Herein, we report the clinical course of a patient with a very mild phenotype of BMD caused by a frameshift mutation, NM_004006.2: c.40_41del GA/p.(Glu14ArgfsX17), in exon 2 of the DMD gene.

scholarly journals Genetic Modifiers of Duchenne Muscular Dystrophy in Chinese Patients

2020 ◽  
Vol 11 ◽  
Author(s):  
Menglong Chen ◽  
Liang Wang ◽  
Yaqin Li ◽  
Yongjun Chen ◽  
Huili Zhang ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Chinese Patients ◽  
Genetic Modifiers

scholarly journals Repression of phosphatidylinositol transfer protein α ameliorates the pathology of Duchenne muscular dystrophy

2017 ◽  
Vol 114 (23) ◽  
pp. 6080-6085 ◽  
Author(s):  
Natassia M. Vieira ◽  
Janelle M. Spinazzola ◽  
Matthew S. Alexander ◽  
Yuri B. Moreira ◽  
Genri Kawahara ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Neuromuscular Diseases ◽  
Genetic Modifiers ◽  
Cardiorespiratory Failure ◽  
Transfer Protein ◽  
Phosphorylated Akt ◽  
Phosphatidylinositol Transfer Protein ◽  
Phosphatidylinositol Transfer ◽  
Dystrophin Protein

Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disease caused by X-linked inherited mutations in the DYSTROPHIN (DMD) gene. Absence of dystrophin protein from the sarcolemma causes severe muscle degeneration, fibrosis, and inflammation, ultimately leading to cardiorespiratory failure and premature death. Although there are several promising strategies under investigation to restore dystrophin protein expression, there is currently no cure for DMD, and identification of genetic modifiers as potential targets represents an alternative therapeutic strategy. In a Brazilian golden retriever muscular dystrophy (GRMD) dog colony, two related dogs demonstrated strikingly mild dystrophic phenotypes compared with those typically observed in severely affected GRMD dogs despite lacking dystrophin. Microarray analysis of these “escaper” dogs revealed reduced expression of phosphatidylinositol transfer protein-α (PITPNA) in escaper versus severely affected GRMD dogs. Based on these findings, we decided to pursue investigation of modulation of PITPNA expression on dystrophic pathology in GRMD dogs, dystrophin-deficient sapje zebrafish, and human DMD myogenic cells. In GRMD dogs, decreased expression of Pitpna was associated with increased phosphorylated Akt (pAkt) expression and decreased PTEN levels. PITPNA knockdown by injection of morpholino oligonucleotides in sapje zebrafish also increased pAkt, rescued the abnormal muscle phenotype, and improved long-term sapje mutant survival. In DMD myotubes, PITPNA knockdown by lentiviral shRNA increased pAkt and increased myoblast fusion index. Overall, our findings suggest PIPTNA as a disease modifier that accords benefits to the abnormal signaling, morphology, and function of dystrophic skeletal muscle, and may be a target for DMD and related neuromuscular diseases.

scholarly journals Validation of genetic modifiers for Duchenne muscular dystrophy: a multicentre study assessingSPP1andLTBP4variants

2014 ◽  
Vol 86 (10) ◽  
pp. 1060-1065 ◽  
Author(s):  
Janneke C van den Bergen ◽  
Monika Hiller ◽  
Stefan Böhringer ◽  
Linda Vijfhuizen ◽  
Hendrika B Ginjaar ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Multicentre Study ◽  
Genetic Modifiers

PULMONARY PARAMETERS CORRELATING WITH CLINICAL COURSE IN DUCHENNE MUSCULAR DYSTROPHY (DMD)

1989 ◽  
Vol 68 (4) ◽  
pp. 205
Author(s):  
Charles C Yang ◽  
Kevin M Satow ◽  
Richard T Albresch ◽  
Robert H Lantz ◽  
William M Fowler ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Clinical Course

scholarly journals The clinical course of Duchenne muscular dystrophy in the corticosteroid treatment era: a systematic literature review

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Shelagh M. Szabo ◽  
Renna M. Salhany ◽  
Alison Deighton ◽  
Meagan Harwood ◽  
Jean Mah ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
North American ◽  
Clinical Course ◽  
Ventilatory Support ◽  
Premature Mortality ◽  
Corticosteroid Treatment ◽  
Neuromuscular Disorder ◽  
Clinical Practices ◽  
The Mean

Abstract Background Duchenne muscular dystrophy (DMD) is a severe rare progressive inherited neuromuscular disorder, leading to loss of ambulation (LOA) and premature mortality. The standard of care for patients with DMD has been treatment with corticosteroids for the past decade; however a synthesis of contemporary data describing the clinical course of DMD is lacking. The objective was to summarize age at key clinical milestones (loss of ambulation, scoliosis, ventilation, cardiomyopathy, and mortality) in the corticosteroid-treatment-era. Methods A systematic review was conducted using MEDLINE and EMBASE. The percentage experiencing key clinical milestones, and the mean or median age at those milestones, was synthesized from studies from North American populations, published between 2007 and 2018. Results From 5637 abstracts, 29 studies were included. Estimates of the percentage experiencing key clinical milestones, and age at those milestones, showed heterogeneity. Up to 30% of patients lost ambulation by age 10 years, and up to 90% by 15 years of age. The mean age at scoliosis onset was approximately 14 years. Ventilatory support began from 15 to 18 years, and up to half of patients required ventilation by 20 years of age. Registry-based estimates suggest that 70% had evidence of cardiomyopathy by 15 years and almost all by 20 years of age. Finally, mortality rates up to 16% by age 20 years were reported; among those surviving to adulthood mortality was up to 60% by age 30 years. Conclusions Contemporary natural history studies from North America report that LOA on average occurs in the early teens, need for ventilation and cardiomyopathy in the late teens, and death in the third or fourth decade of life. Variability in rates may be due to differences in study design, treatment with corticosteroids or other disease-modifying agents, variations in clinical practices, and dystrophin mutations. Despite challenges in synthesizing estimates, these findings help characterize disease progression among contemporary North American DMD patients.

Height and clinical course of Duchenne muscular dystrophy

1989 ◽  
Vol 32 (4) ◽  
pp. 552-552
Author(s):  
J. H. Coakley ◽  
R. D. Griffiths ◽  
R. H. T. Edwards
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Clinical Course

Genetic modifiers of muscle: Studies of college students and Duchenne muscular dystrophy

2015 ◽  
Vol 25 ◽  
pp. S184
Author(s):  
E. Hoffman ◽  
P. Thompson ◽  
C. McDonald ◽  
H. Gordish-Dressman ◽  
L. Bello ◽  
...  
Keyword(s):  
College Students ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Genetic Modifiers

scholarly journals TCTEX1D1 is a genetic modifier of disease progression in Duchenne muscular dystrophy

2020 ◽  
Vol 28 (6) ◽  
pp. 815-825 ◽  
Author(s):  
Pietro Spitali ◽  
◽  
Irina Zaharieva ◽  
Stefan Bohringer ◽  
Monika Hiller ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Disease Progression ◽  
Genetic Modifier ◽  
Chromosome 1 ◽  
European Ancestry ◽  
Candidate Snps ◽  
Genetic Modifiers ◽  
Pathogenic Variants ◽  
Extreme Phenotypes

AbstractDuchenne muscular dystrophy (DMD) is caused by pathogenic variants in the DMD gene leading to the lack of dystrophin. Variability in the disease course suggests that other factors influence disease progression. With this study we aimed to identify genetic factors that may account for some of the variability in the clinical presentation. We compared whole-exome sequencing (WES) data in 27 DMD patients with extreme phenotypes to identify candidate variants that could affect disease progression. Validation of the candidate SNPs was performed in two independent cohorts including 301 (BIO-NMD cohort) and 109 (CINRG cohort of European ancestry) DMD patients, respectively. Variants in the Tctex1 domain containing 1 (TCTEX1D1) gene on chromosome 1 were associated with age of ambulation loss. The minor alleles of two independent variants, known to affect TCTEX1D1 coding sequence and induce skipping of its exon 4, were associated with earlier loss of ambulation. Our data show that disease progression of DMD is affected by a new locus on chromosome 1 and demonstrate the possibility to identify genetic modifiers in rare diseases by studying WES data in patients with extreme phenotypes followed by multiple layers of validation.

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