Clinicopathologic and molecular profiles of Duchenne and Becker muscular dystrophy (original) (raw)
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Neurology India, 2009
Background: Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy that affects young boys and the dystrophin gene on the X chromosome has been found to be associated with the disorder. Materials and Methods: In this prospective study, 112 clinically diagnosed DMD patients had muscle biopsy and were tested for exon deletions. Genotyping was also carried out at STR44, STR45, STR49 and STR 50 markers in 15 families. Results: Of the 112 clinically suspected DMD patients, the diagnosis of DMD was confirmed by histopathology and/or genetics in 101 patients. The mean age of onset was 3.1 6 1.44 years (1-6 years) and the mean age at presentation was 8.0 6 3.1 years (1.1-18.0 years). Delayed motor milestones were present in 63 (62.3%) patients. The mean creatine kinase value was 11822.64 6 8206.90 U/L (1240-57,700). Eighty-four patients had muscle biopsy and immunohistochemistry was done in 60 muscle samples, all of which demonstrated absence of dystrophin staining. Of the 60 dystrophin-negative cases, 73% showed deletion of at least one exon. Single exon deletion was found in 20.4%. Distal hotspot Exons 45, 47, 49 and 50 were the commonly deleted xenons and the deletion rates were 36%, 35%, 33.7% and 38.5% respectively. Conclusions: In this study population in south India the deletion rate was 73% and were more frequent in the distal end exon. With the availability of genetic analysis, the first investigation of choice in DMD should be genetic studies and muscle biopsy should be considered only if the genetic tests are negative or not available.
Journal of Biomedicine and Biotechnology, 2009
Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked recessive disorders caused by mutations of the DMD gene located at Xp21. In DMD patients, dystrophin is virtually absent; whereas BMD patients have 10% to 40% of the normal amount. Deletions in the dystrophin gene represent 65% of mutations in DMD/BMD patients. To explain the contribution of immunohistochemical and genetic analysis in the diagnosis of these dystrophies, we present 10 cases of DMD/BMD with particular features. We have analyzed the patients with immunohistochemical staining and PCR multiplex to screen for exons deletions. Determination of the quantity and distribution of dystrophin by immunohistochemical staining can confirm the presence of dystrophinopathy and allows differentiation between DMD and BMD, but dystrophin staining is not always conclusive in BMD. Therefore, only identification involved mutation by genetic analysis can establish a correct diagnosis.
Duchenne and Becker muscular dystrophy: a molecular and immunohistochemical approach
Arquivos de Neuro-Psiquiatria, 2007
Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are caused by mutations in the dystrophin gene. We studied 106 patients with a diagnosis of probable DMD/BMD by analyzing 20 exons of the dystrophin gene in their blood and, in some of the cases, by immunohistochemical assays for dystrophin in muscle biopsies. In 71.7% of the patients, deletions were found in at least one of the exons; 68% of these deletions were in the hot-spot 3' region. Deletions were found in 81.5% of the DMD cases and in all the BMD cases. The cases without deletions, which included the only woman in the study with DMD, had dystrophin deficiency. The symptomatic female carriers had no deletions but had abnormal dystrophin distribution in the sarcolemma (discontinuous immunostains). The following diagnoses were made for the remaining cases without deletions with the aid of a muscle biopsy: spinal muscular atrophy, congenital myopathy; sarcoglycan deficiency and unclassified limb-girdle muscular dystrophy. Dystrophin analysis by immunohistochemistry continues to be the most specific method for diagnosis of DMD/BMD and should be used when no exon deletions are found in the dystrophin gene in the blood.
Swiss medical weekly, 2006
Both Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are caused by mutations of the X-linked dystrophin gene. BMD patients are less affected clinically than DMD patients. We present five patients with a diagnosis of BMD. First, two identical twins, with a deletion of exon 48 of the dystrophin gene, who experienced prominent muscle cramps from the age of three. The histopathological examination of muscle biopsies of these two twins revealed only very slight muscle fiber alterations. Second, two brothers who displayed marked, unusual intrafamilial variability of the clinical picture as well as showing a new point mutation in the dystrophin gene. And finally, a fifth boy who displayed a new point mutation in the dystrophin gene. Although he was clinically asymptomatic at the age of 15 and muscle biopsy only showed very minor myopathic signs, serum Creatine Kinase (CK) levels had been considerably elevated for years. Taken together, these cases add to the spectrum ...
Mutation Spectrum of Dystrophin Gene in Malaysian Patients with Duchenne/Becker Muscular Dystrophy
Journal of Neurogenetics, 2013
We undertook the clinical feature examination and dystrophin analysis using multiplex ligation-dependent probe amplifi cation (MLPA) and direct DNA sequencing of selected exons in a cohort of 35 Malaysian Duchenne/Becker muscular dystrophy (DMD/BMD) patients. We found 27 patients with deletions of one or more exons, 2 patients with one exon duplication, 2 patients with nucleotide deletion, and 4 patients with nonsense mutations (including 1 patient with two nonsense mutations in the same exon). Although most cases showed compliance to the reading frame rule, we found two unrelated DMD patients with an in-frame deletion of the gene. Two novel mutations have been detected in the Dystrophin gene and our results were compatible with other studies where the majority of the mutations (62.8%) are located in the distal hotspot. However, the frequency of the mutations in our patient varied as compared with those found in other populations.
Patterns of dystrophin gene deletion in Egyptian Duchenne/Becker muscular dystrophy patients
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, 2007
Large variations in the proportion of intragenic deletion in the dystrophin gene have been observed in different populations. Although dystrophin gene deletion was extensively studied all over the world, only few studies were done on Egyptian population and there was no account on the dystrophin gene duplication. In this study, we present our results on the pattern of deletion of the dystrophin gene together with the usage of quantitative polymerase chain reaction (PCR) as a method for duplication analysis within the dystrophin gene in Egyptian patients. Forty one Duchene/Becker muscular dystrophy patients were included in this study. The diagnosis was based on detailed clinical assessment, serum creatine kinase (CK) level, neurophysiologic study and muscle biopsy for histopathological analysis. DNA was extracted from ten milliliter peripheral blood according to basic protocol, and multiplex polymerase chain reaction for dystrophin gene using both Chamberlin and Beggs sets of primer...
Saudi medical journal, 2002
The deletion in the dystrophin gene has been reported for many ethnic groups, but until now the mutations in this gene have not been thoroughly investigated in Saudi patients with Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). We examined the deletion pattern in the dystrophin gene of the Saudi patients applying multiplex-polymerase chain reaction (PCR). The aim of this study is to describe the outcome of our initial effort to identify mutations in the dystrophin gene in a representative group of Saudi patients with DMD and BMD. Genomic deoxyribose nucleic acid was isolated from 41 patients with DMD and BMD (27 patients confirmed by muscle biopsy and 14 patients with clinical suspicion), 3 patients with limb girdle muscular dystrophy, 12 male relatives of the patients, and 5 healthy Saudi volunteers. A total of 25 exons around the deletion prone regions (hot spots) of the dystrophin gene were amplified. The study was carried out at the King Fahad National Gua...
Open Access Macedonian Journal of Medical Sciences
Background: Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked recessive muscular disorders caused by the absence or reduction of the muscle cytoskeletal protein dystrophin. Standard procedures to detect deletion and duplication of the DMD gene use Multiplex Ligation-Dependent Probe Amplification (MLPA). However, genetic testing, such as MLPA, is not covered by the national insurance scheme in Indonesia. Immunohistochemical (IHC) staining of dystrophin from muscle biopsy in the form of Formalin-Fixed Paraffin-Embedded (FFPE) specimens can be an alternative method to detect dystrophin expression in protein levels to establish the diagnosis of DMD or BMD. Objectives: To determinate sensitivity, specificity and accuracy of IHC analysis of dystrophin in DMD/BMD patient in comparison with the standard genetic testing, MLPA. Methods: Twenty-six patients enrolled in this study were clinically diagnosed as DMD/BMD in Dr. Sardjito Hospital and Universitas Gadj...
Neurological Sciences, 2015
Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are the most frequent muscular dystrophies. Present study aimed to determine the frequency of dystrophin gene alterations in Iranian DMD/ BMD patients using molecular techniques. 146 Iranian DMD/BMD patients have been analyzed using two devised sets of multiplex polymerase chain reaction (M-PCR) followed by multiple ligation-dependent probe amplification (MLPA). Two isolated DMD and BMD patients were analyzed by DNA sequencing. 30.9 % of patients had single-exon deletion while group and contiguous exon deletions were identified in 41 % of the patients. The most numerous exon deletions included exons 45-50 and were identified in the first M-PCR set. Deletion detection rate was 99 % in first M-PCR set and remaining deletions (1 %) were identified in the second M-PCR set. MLPA analysis showed that there were two exons 3-5 and 41-43 duplications (1.4 %) in a BMD and a DMD patient, respectively. Two nonsense mutations including c.633dupA and c.6283 C[T were, respectively, found in a DMD and BMD patient in which c.633dupA has not ever been reported in DMD mutation database and was pathogenic mutation. Besides the report of frequency of dystrophin gene alteration in a subset of Iranian DMD/BMD patients, it was revealed that the proposed M-PCR protocol can be useful in the initial step of molecular diagnosis of DMD/ BMD. Exon sequencing would be the final step in determining the mutation status of DMD/BMD patients following MLPA.