Antisense-mediated exon skipping aiming for reading frame restoration is currently a promising therapeutic application for Duchenne muscular dystrophy (DMD). This approach is mutation specific, but as the majority of DMD patients have deletions that cluster in hotspot regions, the skipping of a small number of exons is applicable to relatively large numbers of patients. To assess the actual applicability of the exon skipping approach, we here determined for deletions, duplications and point mutations reported in the Leiden DMD mutation database, which exon(s) should be skipped to restore the open reading frame. In theory, single and double exon skipping would be applicable to 79% of deletions, 91% of small mutations, and 73% of duplications, amounting to 83% of all DMD mutations. Exon 51 skipping, which is being tested in clinical trials, would be applicable to the largest group (13%) of all DMD patients. Further research is needed to determine the functionality of different in-frame dystrophins and a number of hurdles has to be overcome before this approach can be applied clinically.

Theoretic applicability of antisense-mediated exon skipping for Duchenne muscular dystrophy mutations.

This report documents the results of an integrated biochemical and immunocytochemical investigation into the expression of dystrophin (the protein product of the Duchenne muscular dystrophy gene) in muscle biopsies from 226 patients. It is the first study in which dystrophin has been analysed on blots and on tissue sections in such a large number of patients using the same (monoclonal) antibody. The 140 patients with Xp21 muscular dystrophy who were included in this study represent a continuous spectrum of disease severity and this range was reflected in the heterogeneity of dystrophin expression which was observed with respect to abundance, size and the pattern of tissue localisation. Approximately 40% of biopsies obtained from patients diagnosed as having Duchenne muscular, dystrophy (DMD) contained isolated clearly positive fibres and a further 20% had very weak labelling on a large number of fibres. Biopsies from patients with Becker muscular dystrophy (BMD) showed labelling patterns which varied from weak labelling on the majority of fibres to clear labelling on all fibres. Typically, however, there was inter-and intra-fibre variation in labelling intensity. Approximately 85% of the 52 BMD and 54 DMD patients who had unequivocal labelling on blots demonstrated a protein of abnormal size. The remaining 15% had a protein of normal size but reduced abundance. Overall, the estimated abundance of dystrophin correlated well with clinical assessments of the disease severity expressed in patients: We conclude that dystrophin analysis is an essential and dependable technique for the differential diagnosis of patients with Xp21 muscular dystrophy.

Heterogeneity of dystrophin expression in patients with Duchenne and Becker muscular dystrophy

Elevation of serum creatine kinase as the only manifestation of an intragenic deletion of the dystrophin gene in three unrelated families

The rapid progress of research on the structure of the dystrophin gene has enormously increased our understanding of the molecular basis of Duchenne (DMD) and Becker (BMD) muscular dystrophy. Apart from "classical" clinical presentations, asymptomatic or only mildly affected individuals with deletions in the dystrophin gene have now been reported. We describe two families which were initially classified as metabolic myopathies, until the diagnosis of atypical BMD was established after dystrophin analysis at the protein and DNA level. A modern diagnostic approach to myopathies should, therefore, not only include morphological and biochemical investigations, but also be extended to the analysis of the dystrophin gene.

Becker muscular dystrophy: detection of unusual disease courses by combined approach to dystrophin analysis.

Prognostic factors in mild dystrophinopathies

We describe two brothers with identical inherited deletions of one single exon within the middle of the DMD gene; one brother has Becker muscular dystrophy diagnosed at 11 years of age, whereas the older brother is normal at 18. These results have implications for genetic counselling and prenatal diagnosis in families with Becker muscular dystrophy.

A normal male with an inherited deletion of one exon within the DMD gene

Sirs, The distribution of the haplotype (2:l) defined by the two CF-linked markers KM19:XV-2c has been reported to be between 70 and 90% in the European population (Estivill et al. 1987, 1988). Identification and characterization of one mutation causal of CF, delta F508, have made it possible to analyse for the presence of this in affected families (Kerem et al. 1989). This prompted us to investigate a sample of patients from Sweden for the presence of the delta F508 mutation in relation to haplotyping with the CF-linked markers KM19 and xv-2c. A total of 100 non-related CF-patients, representing approximately one third of the Swedish material, have been analysed in the present study, In addition, the distribution of haplotypes on CFchromosomes was investigated in 37 of these families. Blood samples were obtained from the parents and the children. DNA was isolated according to standard procedures and analysed with two CF-linked RFLPs, KM19 and XV-2c. The probeienzyme combination used was KM 19/PstI and XV-2c/TaqI. Oligonucleotide primers sequences and polymerase chain reaction (PCR) conditions were used to detect delta F508. The amplified products were analysed on 12% polyacrylamide gels and stained with ethidium bromide, as described (Rommens et al. 1990). The distribution of chromosomes with and without the mutation and the corresponding genotype are summarized in Table 1. Among the 200 CFchromosomes analysed for delta F508,120 carried the mutation. Hence, the frequency of the mutation on CFchromosomes in our material was

Characterization of the frequency of delta F508 mutation and CF haplotypes in Swedish families.

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Maria Eiserman

Author Tools

Chat about Author

Papers

A normal male with an inherited deletion of one exon within the DMD gene

Characterization of the frequency of delta F508 mutation and CF haplotypes in Swedish families.