Point mutations in the dystrophin gene.
Open Access
- 15 March 1992
- journal article
- case report
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 89 (6), 2331-2335
- https://doi.org/10.1073/pnas.89.6.2331
Abstract
Defining the range of mutations in genes that cause human disease is essential to determine the mechanisms of genetic variation and the function of gene domains and to perform precise carrier and prenatal diagnosis. The mutations in one-third of Duchenne muscular dystrophy patients remain unknown as they do not involve gross rearrangements of the dystrophin gene. The size and complexity of the gene have prohibited the systematic definition of point mutations. We have developed a method for the identification of these mutations by nested amplification, chemical mismatch detection, and sequencing of reverse transcripts of trace amounts of dystrophin mRNA from peripheral blood lymphocytes. Analysis of the entire coding region (11 kilobases) in seven patients has resulted in detection of a sequence change in each case that is clearly sufficient to cause the disease. All mutations should cause premature translational termination, and the resulting phenotypes are thus equivalent to those caused by frameshifting deletions. The results support a particular functional importance for the C-terminal region of dystrophin. Application of this approach to mutation detection will extend direct carrier and prenatal diagnosis to virtually every affected family.Keywords
This publication has 32 references indexed in Scilit:
- Genetics and molecular biology of haemophilias A and BBlood Coagulation & Fibrinolysis, 1991
- Point mutation in the human dystrophin gene: Identification through Western blot analysisGenomics, 1991
- Detection of three novel mutations in two haemophilia A patients by rapid screening of whole essential region of factor VIII geneThe Lancet, 1991
- Direct diagnosis of carriers of Duchenne and Becker muscular dystrophy by amplification of lymphocyte RNAThe Lancet, 1990
- Accurate assessment of intragenic recombination frequency within the Duchenne muscular dystrophy geneGenomics, 1990
- Very mild muscular dystrophy associated with the deletion of 46% of dystrophinNature, 1990
- DIAGNOSIS OF BETA-THALASSAEMIA BY DNA AMPLIFICATION IN SINGLE BLASTOMERES FROM MOUSE PREIMPLANTATION EMBRYOSThe Lancet, 1989
- Primer-Directed Enzymatic Amplification of DNA with a Thermostable DNA PolymeraseScience, 1988
- Complete cloning of the duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individualsCell, 1987
- Single-Step Method of RNA Isolation by Acid Guanidinium Thiocyanate–Phenol–Chloroform ExtractionAnalytical Biochemistry, 1987