Types of MutationsDuchenne is caused by mutations (changes) within the dystrophin gene. A gene is made up of coding regions called exons, and the areas in between exons are called introns. Dystrophin has 79 exons, which makes it one of the largest genes in the body. Show
Making the dystrophin protein from the gene involves several steps. One of the first steps is removing the introns and fitting the exons together, 1-79, like puzzle pieces. If there is a missing piece within the dystrophin gene (deletion) or an extra piece (duplication), your body can have difficulty making dystrophin. What are the most common mutations in the dystrophin gene?Since the dystrophin gene is one of the largest genes in our body, it can frequently acquire mutations (changes). Thousands of different mutations have been reported in the dystrophin gene. It is important to remember that everyone carries mutations in some of our genes, although we usually do not know it because the mutations do not affect us in any noticeable way. This table shows the different types of mutations that can happen in the dystrophin gene, and how common the different mutations occur in people with Duchenne and Becker.
As the table shows, most cases of Duchenne and Becker are caused by large deletions. Continue reading for a brief explanation of each type of mutation:
What is the difference between in-frame vs out-of-frame errors?If you or your child have a deletion mutation, you have probably heard the terms in-frame and out-of-frame. Sometimes this is referred to as the reading frame rule. In-FrameA deletion is in-frame if the reading frame of the gene is preserved and not disrupted, so some dystrophin protein can be made. The protein may be shorter than normal, but it is still functional. In-frame deletions typically result in Becker muscular dystrophy, which usually has a more mild presentation (compared to Duchenne) because there is some dystrophin protein present in the cells. Out-of-FrameA deletion is out-of-frame if the reading frame is completely disrupted, so that no dystrophin protein can be made. Out-of-frame deletions typically result in Duchenne muscular dystrophy, which usually has a more severe presentation (compared to Becker) because there is no dystrophin protein present in the cells. It is important to remember that this reading frame rule is not always perfect. There are some out-of-frame deletions that cause Becker, and some in-frame deletions that cause Duchenne. Sometimes a child’s diagnosis will be “intermediate or unclear” until the child grows older and their progression can be observed. Please speak with your doctor or genetic counselor if you have questions. Can you predict progression based on mutation?Duchenne progresses differently for every person, thus every person living with Duchenne will display their own symptoms despite their genetic mutation. Even siblings with the same mutation may have a very different progression of symptoms. The progression of symptoms through this disease are on a spectrum, from late onset/very mild symptoms to early onset/severe symptoms. Genotype vs. PhenotypeGenotype is a person’s genetic makeup. In Duchenne, it is the genetic mutation that affects the production of dystrophin. Phenotype is how the body chooses to express a specific genotype. In Duchenne, it is the symptoms of how the body is progressing through this diagnosis. It is possible to have a genotype most often associated with Becker, but to have a phenotype more typical of Duchenne, and vice versa. How do you determine what mutation you have?Genetic testing is now the gold standard for the diagnosis of Duchenne and Becker. Genetic testing will determine what type of mutation is present, as well as the specific details of the mutation. Genetic testing can also predict if someone is more likely to have Duchenne or Becker. However, as stated previously, predictions of severity based on the mutation are not perfect and a person’s symptoms and disease progression must also be considered. Therefore, families must consult with their doctor for their final diagnosis. Sometimes there are individuals who are intermediate because their features fall in between Duchenne and Becker. PPMD is able to provide free genetic testing to help eligible individuals determine their mutation through our Decode Duchenne genetic testing program. The application and testing process is fast and easy. Learn more about PPMD’s free genetic testing program. Why is it so important to know your mutation?There are three reasons why it is imperative to know your genetic mutation:
Which of the following changes in an exon is most likely to result in a nonfunctional protein product group of answer choices?What kind of mutation is more likely to result in a nonfunctional protein, a frameshift (resulting from an insertion or deletion) or a point mutation? Silent mutation.
Which of the following mutations is most likely to result in a non functional protein?A frameshift mutation is more likely to result in a nonfunctional protein.
Which type of mutation most likely results in a completely nonfunctional protein quizlet?A frameshift mutation has more effect because after it, all amino acids are altered. Usually a frameshift mutation results in the synthesis of a nonfunctional protein.
Which of the following mutations would most severely affect the protein coded for by a gene?Generally speaking, which of the following mutations would most severely affect the protein coded for by a gene? a frameshift deletion at the beginning of the gene- it would affect every codon after the point where the mutation occurred.
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