scholarly journals Analysis of duplications versus deletions in the dystrophin gene in Serbian cohort with dystrophinopathies

2020 ◽  
Vol 77 (4) ◽  
pp. 387-394
Author(s):  
Jasmina Maksic ◽  
Valerija Dobricic ◽  
Lukas Rasulic ◽  
Nela Maksimovic ◽  
Marija Branakovic ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
De Novo ◽  
Dystrophin Gene ◽  
Becker Muscular Dystrophy ◽  
Severe Form ◽  
De Novo Mutation ◽  
Carrier Status ◽  
Phenotypic Effect ◽  
Exon 2 ◽  
Large Deletions

Background/Aim. Duchenne muscular dystrophy (DMD) and its allelic form Becker muscular dystrophy (BMD) are X-linked diseases that affect males, characterized by progressive muscle and cardiopulmonary weakness, especially in DMD as a severe form of the disease. They result from mutations in the dystrophin gene, and the most common changes are large intragenic deletions and duplications (80%). One third of patients have de novo mutation and 2/3 of the mothers are estimated as carriers. The aim of the study was to analyze the frequency of duplications versus deletions in the dystrophin gene in patients with dystrophinopathies, as well as to analyze the phenotypic effect of large mutations obtained and to determine the carrier status of female relatives in probands with duplications. Methods. We examined 22 DMD and 35 BMD unrelated patients and 6 female relatives of the probands where duplications were found. We used polymerase chain reaction (PCR) and multiplex ligation-dependent probe amplification (MLPA) methods, according to the protocol, to detect or confirm mutations in probands and female carriers. Results. In probands, there were 34 (59.6%) large deletions (mostly affected exons 44?60) and 6 (10.5%) large duplications in 4 DMD and 2 BMD patients. Also, duplications were found in 3 out of 4 (75%) tested mothers. The distribution of duplications was heterogeneous, affecting N-terminal and central rod domain, and included more exons, except for one DMD patient who had duplication of exon 2. An exception from the Monaco rule was present in 9.5% of DMD and 15.8% of BMD probands, i.e. in 12.5% of DMD/BMD cases. Conclusion. In 57 DMD/BMD probands, we found 59.6% of large deletions and 10.5% of large duplications. The most affected region of the DMD gene was the central rod domain. An exception to Monaco''s rule was present in 12.5% of DMD/BMD cases. Three out of 4 examined proband''s mothers were confirmed as carriers.

scholarly journals Pathological evaluation of rats carrying in-frame mutations in the dystrophin gene: a new model of Becker muscular dystrophy

2020 ◽  
Vol 13 (9) ◽  
pp. dmm044701
Author(s):  
Naomi Teramoto ◽  
Hidetoshi Sugihara ◽  
Keitaro Yamanouchi ◽  
Katsuyuki Nakamura ◽  
Koichi Kimura ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Gene Mutations ◽  
Dystrophin Gene ◽  
Becker Muscular Dystrophy ◽  
Severe Form ◽  
Independent Manner ◽  
Glycoprotein Complex ◽  
Dystrophin Expression ◽  
Pathological Evaluation ◽  
Dystrophin Glycoprotein Complex

ABSTRACTDystrophin, encoded by the DMD gene on the X chromosome, stabilizes the sarcolemma by linking the actin cytoskeleton with the dystrophin-glycoprotein complex (DGC). In-frame mutations in DMD cause a milder form of X-linked muscular dystrophy, called Becker muscular dystrophy (BMD), characterized by the reduced expression of truncated dystrophin. So far, no animal model with in-frame mutations in Dmd has been established. As a result, the effect of in-frame mutations on the dystrophin expression profile and disease progression of BMD remains unclear. In this study, we established a novel rat model carrying in-frame Dmd gene mutations (IF rats) and evaluated the pathology. We found that IF rats exhibited reduced expression of truncated dystrophin in a proteasome-independent manner. This abnormal dystrophin expression caused dystrophic changes in muscle tissues but did not lead to functional deficiency. We also found that the expression of additional dystrophin named dpX, which forms the DGC in the sarcolemma, was associated with the appearance of truncated dystrophin. In conclusion, the outcomes of this study contribute to the further understanding of BMD pathology and help elucidate the efficiency of dystrophin recovery treatments in Duchenne muscular dystrophy, a more severe form of X-linked muscular dystrophy.

Dystrophin gene analysis in Hungarian Duchenne/Becker muscular dystrophy families – Detection of carrier status in symptomatic and asymptomatic female relatives

2009 ◽  
Vol 19 (2) ◽  
pp. 108-112 ◽  
Author(s):  
Henriett Pikó ◽  
Viktor Vancsó ◽  
Bálint Nagy ◽  
Zoltán Bán ◽  
Ágnes Herczegfalvi ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Dystrophin Gene ◽  
Becker Muscular Dystrophy ◽  
Gene Analysis ◽  
Carrier Status

Abstract 468: Previously Unrecognized Intronic Variants in the Dystrophin Gene Identified as Possible Contributors to Dilated Cardiomyopathy

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Alex Gyftopoulos ◽  
Tamara Ashvetiya ◽  
Yi-Ju Chen ◽  
Libin Wang ◽  
Charles H Williams ◽  
...  
Keyword(s):  
Heart Failure ◽  
Muscular Dystrophy ◽  
Dilated Cardiomyopathy ◽  
Allele Frequency ◽  
Minor Allele Frequency ◽  
Mixed Model ◽  
Dystrophin Gene ◽  
Becker Muscular Dystrophy ◽  
Minor Allele ◽  
Intronic Variants

Nonischemic dilated cardiomyopathy (DCM) often has a genetic etiology, however, its prevalence and etiologies are not completely understood. The UK Biobank comprises clinical and genetic data for greater than 500,000 individuals with enrollees 40-69 years of age. Our group created a custom phenotype of heart failure using ICD-10 codes for several subtypes of heart failure diagnoses including DCM. We then compared the individuals included in the custom heart failure phenotype to control individuals in a 20-to-1 fashion to identify genetic differences. Data were compared using Mixed Model Analysis for Pedigrees/Populations (MMAP) mixed-model regression. We identified 8 unlinked intronic variants in the dystrophin gene ( DMD ) that, when separated by self-identified race, occurred with a combined minor allele frequency of 0.15 in individuals with heart failure who identified as being of African descent. The combined minor allele frequency of these variants was 0.05 in individuals who self-identified as being of European descent. One variant of DMD in particular (rs139029250), was identified with a minor allele frequency of 0.05 in African British with DCM. The unadjusted odds ratio of a diagnosis of heart failure in individuals with rs129029250 was 4.65. When separated by gender, the unadjusted odds ratios are 2.02 for females and 6.44 for males. DMD is most notably known for its role in Duchenne and Becker muscular dystrophy, both of which are known to cause dilated cardiomyopathy in affected individuals. However, none of the individuals (36 female and 43 male) identified in our analysis with rs129029250 have been diagnosed with Duchenne muscular dystrophy, Becker muscular dystrophy, or a primary disorder of muscle (ICD code G70). Additionally, these individuals have an intronic variant of DMD , while Duchene and Becker muscular dystrophy are both due to exonic mutations. These findings suggest a possible common variant in the DMD gene that may contribute to DCM in individuals of African descent.

scholarly journals Diagnosis of Duchenne/Becker muscular dystrophy and quantitative identification of carrier status by use of entangled solution capillary electrophoresis

1997 ◽  
Vol 43 (5) ◽  
pp. 745-751 ◽  
Author(s):  
Paolo Fortina ◽  
Jing Cheng ◽  
Mann A Shoffner ◽  
Saul Surrey ◽  
Wendy M Hitchcock ◽  
...  
Keyword(s):  
Capillary Electrophoresis ◽  
Muscular Dystrophy ◽  
Genetic Diseases ◽  
Becker Muscular Dystrophy ◽  
Diagnostic Methods ◽  
Carrier Status ◽  
Laser Induced Fluorescence Detection ◽  
General Utility ◽  
Pcr Products ◽  
Quantitative Results

Abstract Use of capillary electrophoresis, a new and useful analytical tool, offers a variety of advantages for nucleic acid analyses, including rapid analysis, automation, high resolution, qualitative and quantitative results, and low consumption of both sample and reagents. We report the first example of the use of entangled solution capillary electrophoresis (ESCE) and laser-induced fluorescence detection (LIF) for separation-based diagnostics in the quantitative analysis of multiplex PCR products for determination of carrier status of Duchenne/Becker muscular dystrophy (DMD/BMD). This ap-proach greatly improved the speed, resolution, and sensitivity of information needed for the diagnosis of DMD/BMD compared with that from conventional diagnostic methods, and is of general utility for diagnosis of genetic diseases.

Proportion and pattern of dystrophin gene deletions in North Indian Duchenne and Becker muscular dystrophy patients

1997 ◽  
Vol 99 (2) ◽  
pp. 206-208 ◽  
Author(s):  
Vinita Singh ◽  
Shirish Sinha ◽  
Sudhish Mishra ◽  
Lakshmi Shankar Chaturvedi ◽  
Sunil Pradhan ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Dystrophin Gene ◽  
Becker Muscular Dystrophy ◽  
Gene Deletions

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.

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