Duchenne muscular dystrophy: A clinical, histopathological and genetic study at a neurology tertiary care center in southern India (original) (raw)
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Objectives: To study the genetic pattern, clinical profile and to find any correlation between them in patients of Duchenne muscular dystrophy. Methods: Patients were selected from Neurogenetic clinic on the basis of clinical features, elevated serum CPK level and electromyographic features. After history and clinical examination, molecular genetic testing was performed by Polymerase Chain Reaction (PCR) technique. Results: Among 100 patients, 73 patients had genetically confirmed disease while 8 cases were proven by biopsy, and thus a total 81 cases were further taken up for the study. Mean age of onset of clinical symptoms was 3.9 yrs; Valley sign and calf hypertrophy were most consistent features, while about 51% had facial weakness. Out of 73 genetically confirmed cases 53 (72.6%) showed deletion in distal exons and 12 (16.4%) showed deletion in both proximal and distal exons while 8 (10.9%) had only proximal deletion. There was no correlation between genetic pattern and clinical features. Conclusion: The positivity of PCR- based diagnosis is higher in our study possibly related to highly selective group of patients. Phenotype and genotype correlation was not seen.
Clinical features of patients with dystrophinopathy sharing the 45-55 exon deletion of DMD gene
Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology / edited by the Gaetano Conte Academy for the study of striated muscle diseases, 2015
Becker muscular dystrophy (BMD) was first described in 1953 by Emile Becker as a benign variant of Duchenne muscular Dystrophy (DMD). Compared with DMD, BMD is clinically more heterogeneous, with initial presentation in the teenage years and loss of ambulation beyond the age of 16 and a wide spectrum of clinical presentations, ranging from only myalgias and muscle cramps to exercise intolerance and myoglobinuria, asymptomatic elevation of serum creatin-kinase, or mild limb-girdle weakness and quadriceps myopathy. About 50% of patients become symptomatic by the age of 10 and the most part by the age of 20 years. However few patients can be free of symptoms till their fifties and cases of late-onset Becker Muscular Dystrophy have also been described. In this report we describe the clinical features of patients with dystrophinopathy sharing a deletion of exons 45-55, occasionally or retrospectively diagnosed. These data are important for both the prognostic aspects of children presenti...
Journal of the Neurological Sciences, 2008
A six year old boy presented with classical features of Duchenne Muscular Dystrophy (DMD) and was confirmed by absent dystrophin staining on muscle biopsy. In the paternal line there were 5 affected individuals across two generations with classical DMD. There was no family history of the illness in the maternal line. Molecular genetics analysis by PCR of the exons showed a deletion in exon 45 in two affected individuals. Microsatellite analysis showed that though the deletion was observed in the same locus in exon 45 it is a new independent mutation.
Journal of Clinical Neuroscience, 2008
We review the clinical status of skeletal involvement and cardiac function in three unrelated patients harboring an in-frame deletion of exons 45 to 55 in the DMD gene followed up for 2 to 7 years. Two younger patients diagnosed as having X-linked dilated cardiomyopathy (XLDCM) developed congestive heart failure without overt skeletal myopathy. Heart failure recurred after viral infection but responded well to diuretics and angiotensin-converting enzyme inhibitors. One older patient diagnosed with Becker muscular dystrophy showed limb-girdle muscular atrophy and weakness at the age of 50, but did not have any cardiac symptoms. Skeletal muscle involvement in each patient remained unchanged, and cardiac function did not worsen in any of the patients during the study. In a younger XLDCM patient, the amount and molecular weight of mutant dystrophin were equally slightly decreased in both skeletal and cardiac muscles. Immunostaining for dystrophin and dystrophin-associated proteins was slightly reduced in both skeletal and cardiac muscle, with no discernible difference between the two. The phenotype of this dystrophinopathy can manifest as XLDCM in younger patients; however, careful attention to cardiac management may result in a favorable prognosis.
Screening of Dystrophin Gene Deletions in Egyptian Patients with DMD/BMD Muscular Dystrophies
Disease Markers, 2000
Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are allelic disorders caused by mutations within the dystrophin gene. Our study has identified 100 Egyptian families collected from the Human Genetics Clinic, National Research Center, Cairo. All cases were subjected to complete clinical evaluation pedigree analysis, electromyography studies, estimation of serum creatine phosphokinase enzyme (CPK) levels and DNA analysis. Multiplex PCR using 18 pairs of specific primers were used for screening of deletion mutations within the dystrophin gene. A frequency of 55% of deletions were found among the families. Sixty per cent of detected deletions involved multiple exons spanning the major or the minor hot spot of the dystrophin gene. The remainder 40% involved single exon deletions, which mainly involved exon 45. Comparing these findings with frequencies of other countries it was found that our figures fall within the reported range of 40%-60% for deletions. The distribution of deletions in our study and other different studies was variable and specific ethnic differences do not apparently account for specific deletions. In addition this study concluded that employment of the 18 exon analysis is a cost effective and a highly accurate (97% detection rate) method to be considered when planning to launch a nationwide program.
Journal of Krishna Institute of Medical Sciences University, 2015
Background: Duchenne Muscular Dystrophy (DMD) is the most common neuromuscular disease of childhood caused by deletion or point mutations in the dystrophin gene. Though the importance of deletion mutations in the dystrophin gene causing DMD have been reported worldwide, no data are available from rural population of Maharashtra. Objectives: This study specifically aimed at the investigation of deletion mutations in the DMD gene from the patients from South-Western Maharashtra. Material & Methods: Fifty patients with clinically diagnosed DMD were analyzed to screen for intragenic deletions in 21 exons within the DMD gene using the multiplex polymerase chain reaction. Results: Amongst the 50 unrelated DMD patients from South-Western Maharashrra we found DMD gene deletions in 47 cases which represent 94 % mutations in DMD patients. Majority of the deletions (85.10%) were located at distal hot spot region that encompasses exons 42-53 and 10.63% of the deletions were located at the proxi...
Molecular Characteristics of Duchenne Muscular Dystrophy in a Lebanese Cohort
Journal of Molecular and Genetic Medicine, 2018
Background: Duchenne Muscular Dystrophy (DMD) is a progressive neuromuscular disorder characterized by a relentless clinical course with diagnosis usually established around three to four years of age. DMD is caused by mutations in the dystrophin gene, where deletions and duplications of one or more exons represent the bulk of related genetic aberrations. Aims and methods: Our aim in the current study is to analyze the frequency and the distribution pattern of deletions/duplications associated with dystrophin gene exons and assess the mean diagnostic age of DMD in a small Lebanese group of dystrophic patients suspected with DMD/BMD based on observed clinical features. Results and discussion: Among 52 samples analyzed, we identified 33 cases (63%) with deletions and two cases (4%) with duplications. Deletions were of variable sizes, ranging from 1 to 47 exons and occurred mostly (78%) in two deletion hotspots (HS), HS1 (18%) and HS2 (60%), covering exons 6-19 and 45-52 respectively. Single exon deletions were even further restricted (90%) to the deletion hotspots, mainly to HS2 (80%). The average age of DMD molecular diagnosis in our subject study was 7 years of age. Conclusion: Molecular analyses were consistent with those obtained in previous studies, with however an average age of DMD diagnosis significantly later than what is usually reported. Our study illustrates the need to implement early molecular diagnosis in order to institute optimal care, including available targeted treatments, for our patients.
Biotechnology Journal International
Duchenne Muscular Dystrophy (DMD) is a genetic disorder involving progressive muscle deterioration leading to loss of mobility, cardiomyopathy, and respiratory complications leading to an early death by the fourth decade of life. Males are affected more often as DMD results from a mutation in the dystrophin gene residing on the X chromosome. The DMD genetic mutation results in a complete functional lack of dystrophin, which culminates as an inadequate connection between the intracellular actin filaments and the extracellular skeleton of muscle. Boys affected by DMD clinically present with muscle weakness before age five, are often wheelchair-bound by age 12, and rarely survive beyond the third decade of life. Traditional treatment strategies have focused primarily on quality-of-life improvement and have included the use of glucocorticoids and physical therapy. No cure currently exists, however many novel treatments for DMD are currently being explored. Some of these involve gene the...
Deletion analysis of Duchenne muscular dystrophy
The Turkish journal of pediatrics
DNA of 15 patients with Duchenne muscular dystrophy (DMD) were analyzed for deletions within the DMD gene by using recombinant DNA technology. Deletion frequency was 47 percent and six of the deletions occurred in the region of probe 7 + 8. Only one of the deletions was observed in the region of probe 9-7, and no deletions were found in the region of probe 30-1, 30-2 and 47-4 (5b + 6). The frequency of deletions found in the Turkish DMD patients corresponds to frequencies reported for other populations.