R Jamuna

Bio: R Jamuna is an academic researcher from National Institute of Mental Health and Neurosciences. The author has contributed to research in topics: Duchenne muscular dystrophy & Muscular dystrophy. The author has an hindex of 1, co-authored 1 publications receiving 27 citations.

Duchenne muscular dystrophy: A clinical, histopathological and genetic study at a neurology tertiary care center in southern India

Abstract: 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±1.44 years (1-6 years) and the mean age at presentation was 8.0±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±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.

Duchenne Muscular Dystrophy and Becker Muscular Dystrophy Confirmed by Multiplex Ligation-Dependent Probe Amplification: Genotype-Phenotype Correlation in a Large Cohort

Abstract: Background and purpose Studies of cases of Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) confirmed by multiplex ligation-dependent probe amplification (MLPA) have determined the clinical characteristics, genotype, and relations between the reading frame and phenotype for different countries. This is the first such study from India. Methods A retrospective genotype-phenotype analysis of 317 MLPA-confirmed patients with DMD or BMD who visited the neuromuscular clinic of a quaternary referral center in southern India. Results The 317 patients comprised 279 cases of DMD (88%), 32 of BMD (10.1%), and 6 of intermediate phenotype (1.9%). Deletions accounted for 91.8% of cases, with duplications causing the remaining 8.2%. There were 254 cases of DMD (91%) with deletions and 25 (9%) due to duplications, and 31 cases (96.8%) of BMD with deletions and 1 (3.2%) due to duplication. All six cases of intermediate type were due to deletions. The most-common mutation was a single-exon deletion. Deletions of six or fewer exons constituted 68.8% of cases. The deletion of exon 50 was the most common. The reading-frame rule held in 90% of DMD and 94% of BMD cases. A tendency toward a lower IQ and earlier wheelchair dependence was observed with distal exon deletions, though a significant correlation was not found. Conclusions The reading-frame rule held in 90% to 94% of children, which is consistent with reports from other parts of the world. However, testing by MLPA is a limitation, and advanced sequencing methods including analysis of the structure of mutant dystrophin is needed for more-accurate assessments of the genotype-phenotype correlation.

MLPA identification of dystrophin mutations and in silico evaluation of the predicted protein in dystrophinopathy cases from India.

Abstract: Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked recessive disorders caused by mutations in the DMD gene. The aim of this study was to predict the effect of gene mutations on the dystrophin protein and study its impact on clinical phenotype. In this study, 415 clinically diagnosed patients were tested for mutations by Multiplex ligation dependent probe amplification (MLPA). Muscle biopsy was performed in 34 patients with negative MLPA. Phenotype-genotype correlation was done using PROVEAN, hydrophobicity and eDystrophin analysis. We have utilized bioinformatics tools in order to evaluate the observed mutations both at the level of primary as well as secondary structure. Mutations were identified in 75.42% cases, of which there were deletions in 91.6% and duplications in 8.30%. As per the reading frame rule, 84.6% out-of frame and 15.3% in-frame mutations were noted. Exon 50 was the most frequently deleted exon and the exon 45–52 region was the hot-spot for deletions in this cohort. There was no correlation noted between age of onset or creatine kinase (CK) values with extent of gene mutation. The PROVEAN analysis showed a deleterious effect in 94.5% cases and a neutral effect in 5.09% cases. Mutations in exon 45–54 (out of frame) and exon 46–54 (in-frame) regions in the central rod domain of dystrophin showed more negative scores compared to other domains in the present study. Hydrophobicity profile analysis showed that the hydrophobic regions I & III were equally affected. Analysis of deletions in hinge III hydrophobic region by the eDystrophin programme also predicted a hybrid repeat seen to be associated with a BMD like disease progression, thus making the hinge III region relatively tolerant to mutations. We found that, while the predictions made by the software utilized might have overall significance, the results were not convincing on a case by case basis. This reflects the inadequacy of the currently available tools and also underlines the possible inadequacy of MLPA to detect other minor mutations that might enhance or suppress the effect of the primary mutation in this large gene. Next Generation Sequencing or targeted Sanger sequencing on a case by case basis might improve phenotype- genotype correlation.

Duchenne/Becker muscular dystrophy: A report on clinical, biochemical, and genetic study in Gujarat population, India.

Abstract: Objective: In India, various groups have studied different regions to find out deletion pattern of dystrophin gene. We have investigated its deletion pattern among Duchenne/Becker muscular dystrophy (D/BMD) patients across Gujarat. Moreover, in this study we also correlate the same with reading frame rule. However, we too consider various clinicopathological features to establish as adjunct indices when deletion detection fails. Materials and Methods: In this pilot study, a total of 88 D/BMD patients consulting at our centers in Gujarat, India were included. All patients were reviewed on basis of their clinical characteristics, tested by three primer sets of 10-plex, 9-plex, and 7-plex polymerase chain reaction (PCR) for genetic analysis; whereas, biochemical indices were measured using automated biochemical analyzers. Results: The diagnosis of D/BMD was confirmed by multiplex-PCR (M-PCR) in D/BMD patients. A number of 65 (73.86%) out of 88 patients showed deletion in dystrophin gene. The exon 50 (58.46%) was the most frequent deletion found in our study. The mean age of onset of DMD and BMD was 4.09 ΁ 0.15 and 7.14 ΁ 0.55 years, respectively. In patients, mean creatine phosphokinase (CPK), lactate dehydrogenase (LDH), and myoglobin levels were elevated significantly ( P Conclusion: The analysis has been carried out for the first time for a total of 88 D/BMD patients particularly from Gujarat, India. More research is essential to elucidate specific mutation pattern in association with management and therapies of proband.

Genetic and Clinical Profile of Patients of Duchenne Muscular Dystrophy: Experience from a Tertiary Care Center in Eastern India.

Abstract: Objectives To study the genetic pattern, clinical profile and to find any correlation between them in patients of Duchenne muscular dystrophy.

Mutation pattern in 606 Duchenne muscular dystrophy children with a comparison between familial and non-familial forms: a study in an Indian large single-center cohort

Abstract: Duchenne muscular dystrophy (DMD) is induced by a wide spectrum of mutations such as exon deletions, duplications and small mutations in the dystrophin gene. This is the first study on the mutational spectrum in a cohort of DMD children from India, with an emphasis to compare the mutations in familial and sporadic forms. Multiplex ligation-dependent probe amplification (MLPA) and next-generation sequencing (NGS) identified 525 and 70 cases of DMD, respectively, while 11 cases showed absent dystrophin staining with no mutations detected. Families with two or more affected males contributed to 12% of the entire cohort. The mutations comprised of exonic deletions in 492/606 (81.2%), duplications in 33/606 (5.4%) and small mutations (point mutations and INDELs) in 70/606 (11.5%) cases. MLPA identified significantly more larger mutations in sporadic (88.2%) than in familial cases (75.3%). The mutations in NGS were: [nonsense = 40 (57.1%); frameshift = 17 (24.3%); splice variant = 12 (17.1%)]. Nonsense mutations were more common in familial than in sporadic cases: 17.8% vs 10.7%. The familial group reported an earlier onset of disease (2.8 ± 1.7 years) as compared to sporadic cases (3.8 ± 1.6 years). MLPA could identify mutations in a high percentage of our DMD children. The preponderance of small mutations was noted to be distinctly higher in the familial group. Intriguingly, the familial form of DMD formed a small percentage of the entire cohort. The reasons could be increasing awareness among parents and physicians with early identification of DMD cases, genetic counseling and prenatal testing.