Thursday 7 January 2010
Research could predict age of onset of heart problems in Becker muscular dystrophy
Analysing the DNA of individuals with Becker muscular dystrophy could be used to predict when they will begin to develop heart problems, US researchers report. Depending on the kind of mutation an individual carries in the dystrophin gene, the age at which they are likely to develop heart problems can vary from mid-20s to mid-40s, the researchers found. If these findings are borne out in further research, clinicians may be able to to identify people at high risk of developing heart problems and prescribe them cardioprotective drugs in good time, before the symptoms of heart problems become apparent.
Becker muscular dystrophy is caused by mutations in the gene which contains the instructions for the production of dystrophin protein. Dystrophin is an important component of muscle fibres throughout the body, including in the heart. In Becker muscular dystrophy, these mutations can result in the production of an altered form of dystrophin. Such mutations can come in many different forms, which is why people with Becker muscular dystrophy vary in the severity of their condition, its rate of progression and age of onset.
Heart problems are a particular risk for people with Becker muscular dystrophy - about 70% develop heart problems due to a condition called dilated cardiomyopathy. Heart failure is the primary cause of death among individuals with Becker muscular dystrophy.
Heart problems in people with Becker muscular dystrophy often don't have any symptoms in the early stages, so any means of identifying those at risk of developing heart problems in the near future will greatly aid clinicians in their efforts to prevent premature deaths.
Contents
- What does this new research show?
- What does this mean for patients?
- Background information
- Further information and links
What does this new research show?
The researchers studied data from 118 people with either Becker muscular dystrophy or X-linked distal cardiomyopathy (a condition in which mutations in the dystrophin gene causes heart problems but not muscle weakness in the rest of the body). They divided the 78 patients with cardiomyopathy into three groups depending on the type of mutation they were found to have.
The researchers found that the 11 patients in the first group with deletion mutations affecting parts of the beginning of the dystrophin gene (exons 2 to 9) had the earliest age of onset of symptoms of dilated cardiomyopathy, at a median of 23 years of age.
In comparison, the 67% of patients in the second group with deletions towards the end of the dystrophin gene (exons 45 to 49) that preserve part of the dystrophin protein called 'hinge 3' had a later age of onset, at a median of 29.5 years.
An even later median age of onset of 43 years was found among the 11 patients in the third group with deletions towards the end of the dystrophin gene (exons 45 to 55) that remove or disrupt 'hinge 3' in the dystrophin protein.
Further analysis showed that patients in the second group could be divided by the precise nature of their mutation into two sub-groups with respective median ages of onset of 26 years and 36 years.
What does this mean for patients?
The researchers showed that a Becker muscular dystrophy patient's type of gene mutation can be used to predict when they are likely to develop dilated cardiomyopathy. As heart failure is the most common cause of death among patients with Becker muscular dystrophy, any extra information physicians can get to help them determine a patient's risk of developing heart problems will be of great benefit. If a patient can be given cardioprotective drugs before dilated cardiomyopathy manifests itself, the risk of premature death will be reduced compared to if the drugs are only given once the symptoms of dilated cardiomyopathy are apparent.
Further studies involving more patients and looking at the relationships between specific mutations and age of onset of cardiomyopathy will empower clinicians to use genetic information to intervene more effectively in the treatment of patients with Becker muscular dystrophy or X-linked dilated cardiomyopathy.
The findings from this study also pave the way for improvements on current therapeutic approaches targeting the heart in Becker muscular dystrophy and X-linked dilated cardiomyopathy, and may be valuable for grouping patients according to their risk of heart problems in clinical trials.
Background
Becker muscular dystrophy resembles Duchenne muscular dystrophy, but is less severe. It is a genetic disorder caused by mutations in the dystrophin gene. This gene contains the instructions for the dystrophin protein, which normally sits in the membrane that surrounds muscle fibres and protects them from damage during muscle contraction. Consequently, in Becker muscular dystrophy, the muscle fibre membranes become damaged and eventually break down, causing progressive muscle weakness.
Further information and links
Read more about Becker muscular dystrophy
The full original paper published in Circulation Cardiovascular Genetics is available by subscription only. The article is written in technical language with no summary in layman's terms. The reference for the paper is:
Kaspar RW et al. Analysis of Dystrophin Deletion Mutations Predicts Age of Cardiomyopathy Onset in Becker Muscular Dystrophy. Circ Cardiovasc Genet. 2009 Sep 30.
