Milder Clinical Features Associated with a Specific Deletion in the Dystrophin Gene

Patrícia Silva, PhD avatar

by Patrícia Silva, PhD |

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Researchers at the Second University of Naples in Italy recently described the clinical characteristics of patients with a specific deletion in the dystrophin gene. The study was published in the journal Acta Myologica and is entitled “Clinical features of patients with dystrophinopathy sharing the 45-55 exon deletion of DMD gene”.

Muscular dystrophies are characterized by a progressive skeletal muscle weakness that leads to the degeneration of muscle cells and tissues, compromising locomotion. It can also affect specific muscles involved in the respiratory function, leading to breathing complications and cardiac problems. Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are two muscular dystrophies caused by mutations in the dystrophin gene. DMD has a rapid progression and a more severe phenotype than BMD, with the majority of patients requiring a wheelchair by the age of 12 and often succumbing to the disease in their 20s. BMD has a milder phenotype, with initial presentation in the teenage years, loss of ambulation beyond the age of 16 and a near-normal life expectancy. Both disorders affect mainly boys.

BMD has a wide range of clinical presentations, from asymptomatic forms, muscle pain (myalgia) and cramps to exercise intolerance, myoglobinuria (myoglobin in the urine, a sign of muscle destruction), mild limb-girdle and quadriceps myopathy (muscle weakness), and cardiac involvement.

The dystrophin gene has 79 exons (coding units) and contains two deletion hot-spots, regions with a high propensity to suffer deletions, one of them the region between exons 45 and 55. In the study, researchers describe the clinical features of patients with this specific deletion in the dystrophin gene, including data on nine patients diagnosed at the Second University of Naples.

According to the authors, patients with deletion of dystrophin exons 45-55 seem to have a favorable prognosis with a less severe muscular involvement, and only a few cases of dilated cardiomyopathy (disorder in which the heart becomes enlarged and unable to pump blood efficiently). The severity of cardiac involvement may be independent on the severity of skeletal muscle damage. Interestingly, researchers found that deletions of exons 48-49 in BMD patients results in a more severe cardiac involvement. At the muscular level, all patients examined exhibited quadriceps hypotrophy (progressive degeneration due to the loss of muscle cells) and calf hypertrophy (increase in size of skeletal muscle through a growth in cell size).

Establishing the clinical phenotype of BMD patients with deletion of exons 45-55 in the dystrophin gene is important as it is usually associated with a mild, benign prognosis, requiring less follow-up visits and less aggressive therapies than other types of mutations. Recognizing the exon 45-55 deletion is also relevant in terms of genetic counseling, so that families can be reassured on the benign course of the disease. The authors also emphasize that clinicians should be aware of a possible BMD diagnosis in asymptomatic adult individuals experiencing mild hyperckemia, high levels of creatine kinase in the blood (usually a sign of a muscle disease) but without muscle weakness symptoms.