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Table of Contents    
Year : 2021  |  Volume : 69  |  Issue : 4  |  Page : 797-807

Challenges and Advances in Molecular Diagnosis of Myopathies and Dystrophies in Perspective of Their Use in Developing Countries: Past, Present, and Future

Department of Biotechnology, Chaudhary Devi Lal University, Sirsa, Haryana, India

Date of Submission02-Sep-2020
Date of Decision12-Jul-2021
Date of Acceptance12-Jul-2021
Date of Web Publication2-Sep-2021

Correspondence Address:
Shivangi Attri
Department of Biotechnology, Chaudhary Devi Lal University, Sirsa - 125 055, Haryana
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.325313

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 » Abstract 

Background: Proper diagnosis is the first and most critical step for effective identification and treatment of myopathy and dystrophy disorders. Although various histochemical and biochemical studies have paved the way for efficient testing of these disorders, they are insufficient for accurate diagnosis. To overcome this, the diagnostic procedure has now shifted more toward the “genetic first approach,” with the remarkable role played by various genetic and molecular techniques.
Objective: In developing countries, successful diagnosis of such disorders is affected by the shortage of hospitals, poor lab setup, limited diagnostic methods, and unavailability of technical expertise. As a major population living in developing countries faces such inadequate healthcare facilities, there has always been a need for identifying effective diagnostic techniques that could identify genetic alterations more prone in such regions.
Materials and Methods: This article reviews studies done in the last few years that primarily use nonsequencing-based molecular diagnosis methods to identify myopathy- and dystrophy-specific gene alterations and thus could equally hold potential for screening key genetic alterations reported in certain regions in developing countries. Further, this review deals with new emerging sequencing and next-generation sequencing (NGS)-based approach and their potential in providing an adequate diagnosis.
Conclusions: This study promotes nonsequencing-based molecular methods to be an effective method for early-stage diagnosis and management of myopathies and dystrophies in developing countries and suggests the high importance of emerging NGS methods in proper diagnosis and identifying new players in neuromuscular disorders.

Keywords: Diagnosis, dystrophy, genetics, GNE, myopathy
Key Message: Accumulating knowledge clearly shows a higher frequency of certain genetic mutations inducing neuromuscular disorders in specific populations. Identifying and screening such markers using molecular technologies may better manage patients prone to such diseases in developing countries.

How to cite this article:
Attri S, Gahlawat SK. Challenges and Advances in Molecular Diagnosis of Myopathies and Dystrophies in Perspective of Their Use in Developing Countries: Past, Present, and Future. Neurol India 2021;69:797-807

How to cite this URL:
Attri S, Gahlawat SK. Challenges and Advances in Molecular Diagnosis of Myopathies and Dystrophies in Perspective of Their Use in Developing Countries: Past, Present, and Future. Neurol India [serial online] 2021 [cited 2021 Oct 22];69:797-807. Available from:

Myopathies are a collection of genetic alterations that ultimately leads to abnormal structure or functioning of skeletal muscles.[1],[2] Apart from managing treatment after symptomatic detection, their timely screening and diagnosis can help in better management.[3],[4] Further, late diagnosis and delay in proper management of such patients can also affect appropriate treatment.[5],[6],[7],[8],[9],[10] With the rapid advancement in myopathy research in the last few decades, we can now establish region- and subcontinent-wise prevalence and molecular variations in myopathies and dystrophies.[11],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22],[23],[24],[25] For example, more than 200 mutations have been reported in GNE myopathy; however, some of these SNPs are more prevalent in Japan, China, Middle East, and the Roma population in Bulgari and UK.[26],[27] Consequently, accumulating knowledge clearly shows the frequency of many mutations inducing other myopathies and dystrophies, showing a trend toward the population in certain regions. Thus, such mutations can be used for timely detection of myopathies and dystrophies in families that have a history of such disorders or could be carriers for the next generation.[6],[8],[10]

Molecular alterations associated with myopathy

Various key genetic alterations responsible for myopathies have been identified in the last few decades.[1],[11],[28],[29],[30],[31],[32],[33],[34] To identify these mutation patterns specific to myopathies and dystrophies, we first looked for a publicly available “ClinVar” database for reported genetic alterations. We used the search terms “OMIM” [submitter] and “dystrophy” [disease/phenotype] or “myopathy” [disease/phenotype] for our analysis. This led to the identification of 499 gene variants across various genes previously correlated with myopathy and 1028 gene variants associated with dystrophy [Table 1]. Interestingly, single nucleotide variation was seen in majority of studies that represented 83.8% (418/499 cases) of myopathies and 77.5% (797/1028) dystrophy cases. Findings from this cohort suggest the prevalence of single nucleotide variations across these disorders and suggest the importance of screening diseased and carrier populations in any susceptible population cohort. As covering methods to detect all these mutations are beyond the scope of this review article, we focused on known genetic mutations, especially in context but not limited to hereditary myopathies, whose large types are well reported in the literature[2],[6],[29],[30],[34],[35],[36],[37] [Table 2]. We also discuss muscular dystrophies, which are generally characterized by pathological evidence of ongoing muscle degeneration and regeneration.[2],[37],[38] This review explores some of the key nonsequencing molecular methods used in screening in past decades, some of which still hold a strong potential, especially for use under low-cost clinical setups in developing countries for timely screening of hotspot mutations prevalent in a population. In addition, this study discusses the next-generation sequencing (NGS) methods that hold great potential in the coming future.
Table 1: List of genetic alterations reported in the “ClinVar” database for various myopathic and dystrophic alterations

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Table 2: Details of hereditary myopathies and dystrophies and their mechanism, associated features, and key genes affected

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 » Nonsequencing Molecular Methods and Their Screening Potential Top

Amplification refractory mutation system

Amplification refractory mutation system (ARMS-PCR) is a general technique used for detection of any point mutation or small deletion, which are some of the commonly found genetic alterations.[39] This technique may detect normal, heterozygous, and homozygous states in the genotype of a sample using two complementary reactions, including specific primers for the amplification of typical DNA sequence at a given locus and other primers containing a mutant specific primer for the amplification of mutant DNA [Table 3]. In recent decades, these techniques have been used to detect both myopathy and dystrophy cases. In one such study by Fanim M et al.[40] (2004), ARMS-PCR in combination with other techniques (including SSCP, DHPLC, and direct sequencing) was used to detect mutation in the LGMD2A mutation cohort. In recent years, this technique has also been used to evaluate sequence variants in the patient, carrier, and fetus for detecting a nonsense variant (c.C799T: p.R267X) in the CHM gene.[41] Bai RK (2004)[42] and Attali R et al. (2013)[43] used the ARMS-PCR method for detection of mitochondrial and congenital myopathy, respectively. Bai RK specifically analyzed for A3243G mitochondrial tRNAleu (UUR) point mutation in 36 patients.[42] Interestingly, this study demonstrated consistent results between PCR-restriction fragment length polymorphism (RFLP) analysis and real-time ARMS-qPCR. However, the findings of this study also showed ARMS-qPCR method was much more sensitive for detecting low percentages of mutant heteroplasmy. Attali R used the ARM-PCR approach along with Genome-wide linkage and sequencing techniques to screen congenital myopathy-specific mutations in a family using healthy individuals as controls.[43] Collectively, these studies indicate that the ARMS-PCR technique can be used as a potential molecular tool in diagnosing genetic diseases in prenatal, newborns, and adults.
Table 3: List showing key advantages and disadvantages of various molecular methods used to diagnose myopathies and dystrophies

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Nested PCR

Nested PCR uses two or more successive PCRs, where the product of the initial PCR reaction is used as a template for the next PCR. This type of PCR is employed to amplify templates in low copy numbers in specimens. It has the benefits of increased sensitivity and specificity [Table 3]. In the past few years, this technique has also been used to screen various forms of myopathies. Huang W et al. (2004)[44] and Malcov (2005) et al.[45] used nested PCR to analyze dystrophin and SRY gene as well as to evaluate the possibility of using this technique for pre-implantation genetic diagnosis (PGD) of deleted Duchene muscular dystrophy (DMD) with family history. Huang W et al.[44] reported that this technique of single lymphocytes 3-plex nested PCR for dystrophin and SRY gene was highly sensitive and reliable for PGD of deleted DMD with family history. Similarly, Malcov et al.[45] analyzed biopsies of 156 embryos and was found them to be reliable in DMD diagnosis. Nested PCR was also used by Fardeau M et al. (2005)[46] to check transgene expression and safety of intramuscular administration of a plasmid containing a full-length dystrophin cDNA. Gergely P and Joshi PR also used nested PCR for idiopathic inflammatory and myofibrillar myopathies.[47] Interestingly, Gergely P et al. assessed the prevalence of TTV infection in IIM compared to patients with rheumatoid arthritis and healthy blood donors.[47] However, Joshi PR used it for microdissected fibers analysis for multiple mtDNA deletions.[48] These studies demonstrated the effective use of nested PCR to diagnose and screen myopathy and dystrophy-associated patients.

Restriction fragment length polymorphism

RFLP technique was invented in 1984 by Alec Jeffreys and was later widely used for the analysis of Variable Number of Tandem Repeats to genetically differentiate between organisms. This technique has also been used to study genetic variation in various myopathies and dystrophies due to its advantages [Table 3]. In the last few decades, this technique, either alone or in combination with other techniques, has been used widely. In one such study by Scuderi C et al.,[49] RFLP and DNA sequence analyses revealed pathogenic mutations m. 3243A > G in muscle and blood and a new heterozygous insertion at nt697 in doublecortin gene (DCX). In work done by Shojasaffar B et al.,[50] a healthy population in Iran was analyzed for CTG expansion and haplotype analysis in DM1 gene in a healthy Iranian population using PCR/RFLP from control healthy individuals. In another study on McArdle disease (a metabolic myopathy) by Rubio JC et al.,[51] RFLP along with other techniques was used to study 55 unrelated Spanish patients with McArdle disease for screening for three more frequent mutations in the PYGM gene in the Spanish population. Interestingly, the findings of this study suggest that molecular diagnosis of disease based on blood DNA would avoid muscle biopsy in 75.8% [95% confidence interval (95% CI): 62.1%–78.6%] of patients with McArdle disease. In another study by Cardaioli E et al.[52] on mitochondrial myopathy, RFLP analysis confirmed that 63% of muscle mtDNA harbored mutation while it was absent in all other tissues. In another study by Malayeri FA et al.[53] on DMD and BMD dystrophies, six RFLP markers were used for carrier detection and prenatal diagnosis in patients and their family members in the Iranian population. Interestingly, the group reported that linkage analysis using these six RFLP markers for carrier detection and the prenatal diagnosis was a rapid, easy, reliable, and inexpensive method, suitable for most routine diagnostic services. In another study by Wojcik KA et al.[54] in keratoconus (KC) and Fuchs endothelial corneal dystrophy (FECD) that included 279 patients with KC, 225 patients with FECD and 322 control individuals were studied. The group reported an association between two SNPs, c.-441G > A (rs174538) and g. 61564299G > T (rs4246215), in the FEN1 gene using PCR and RFLP techniques. Interestingly, this group reported that SNP g. 61564299G > T and c.-441G > A polymorphisms in the FEN1 gene can modulate the risk of keratoconus and FECD. Further, in a recent study by Foja S et al.,[55] RFLP was used to study novel missense mutations of cornea-specific TGFBI gene in patients and two generations of a family diagnosed with unique corneal dystrophy phenotypes. This group reported two novel mutations: c. 1640T > G (p.Phe574Cys) in exon 12 and c. 393G > T (p.Glu131Asp) in exon 4 of TGFBI gene. Thus, RFLP seems to be a very relevant molecular method that has also been used in recent years to study the molecular cause of various critical myopathies and dystrophies.

Multiplex ligation-dependent probe amplification

Multiplex ligation-dependent probe amplification (MLPA) is a multiplex polymerase chain reaction-based method that can simultaneously detect changes in gene copy number status, DNA methylation, and point mutations. MLPA can be performed using a standard thermocycler and capillary electrophoresis equipment, thus making it a robust, reliable, and cost-effective method [Table 3]. Moreover, the procedure requires a short working time and results can be obtained in one day. MLPA can also be used on highly fragmented DNA as probes used in this procedure bind to a sequence of only 50–100 nucleotides in length. Hence, this technique is good for the detection of small deletions encompassing only a single exon. As nearly 50 different genomic locations can be tested in a single reaction, it is a reliable method for detecting genetic alterations of diagnostic and prognostic significance in various myopathies and dystrophies. In the past few decades, MLPA has been used in numerous studies that specially focused on dystrophies.[56],[57],[58],[59],[60] In two such studies by Tallapaka K et al.[56] and Polavarapu K et al.[57] in India, 510 and 606 patients were analyzed, respectively, for dystrophies using MLPA and sequencing methods. Interestingly, a study by Polavarapu K et al. reported MLPA to be identifying significantly larger mutations in sporadic (88.2%) than in familial cases (75.3%). A study by Tallapaka et al. showed that MLPA detected mutation in the DMD gene in 372/510 (72.9%), of whom 342 (67.1%) had exonic deletions and 30 (5.9%) had exonic duplications. Similar studies in China by Zhao HH et al.[58] and Kong X et al.[59] showed the importance of MLPA based diagnosis in detecting muscular disorders. Zhao HH reported MLPA to have better productivity and sensitivity than multiplex PCR, whereas studies by Kong X showed that a combination of MLPA, NGS, and Sanger sequencing is of great significance for family analysis, gene diagnosis, and gene therapy. Thakur N et al.[60] and Mohammed F et al.[61] also used MLPA to report DMD mutation patterns in Sri Lankan and Kuwait populations, respectively. Overall, there are a large set of studies that have shown the importance of MLPA in the diagnosis and screening of neuromuscular disorders.

Multiplex PCR

Multiplex PCR is a highly sensitive and specific test for detection and proper diagnosis in patients with Duchenne and Becker muscular dystrophy (DMD and BMD). This method is effective in DMD because a majority of DMD-associated mutations are deletions. Thus, rapid polymerase chain reaction (PCR) assays can be easily developed for deletion detection in patients in a day. This method provides multiple advantages in diagnosis [Table 3]. Literature suggests a high-level use of this method for DMD/BMD detection. This method has widely been used in combination with MLPA for effective patient diagnosis. However, many groups have found it effective as an individual detection method. In one such study in India, Kumari P et al.[62] studied 225 samples for deletion from 25 exons of DMD gene using multiplex PCR. They found that deletions were present in 169 (75.1%) patients of DMD/BMD, with the most frequent deletions observed in exon 50 (14.9%) and exon 49 (10.8%). Another study by Li Y et al.[63] on 239 DMD patients reported that multiplex PCR is an effective tool for identifying alterations in 19 exons. In a study by Sedghi M et al.,[64] the efficiency of MLPA and multiplex PCR was analyzed. This study reported that MLPA analysis can determine all deletions detected by multiplex PCR and suggested that multiplex PCR might be used for initial analysis of boys affected with DMD in the Iranian population as it can detect 95% of rearrangements in patients with DMD. However, few studies have modified multiplex PCR for rapid and accurate diagnosis of DMD. In one such study by Syu JR et al.,[65] a short-end injection CE (short-end CE) was used after PCR that speeded up genotyping of the DMD gene. This method involved no extra purification and was completed within 9 min, with results showing good agreement with those of MLPA. Overall, multiplex PCR holds a promising approach for the diagnosis of DMD/BMD in patients that has promising diagnostic importance.

Future challenges in using nonsequencing methods

Nonsequencing-based molecular techniques have faced some drawbacks that limit their use in many labs [Table 3]. One of the major limitations with most of these is the variation of standardization from lab to lab. Further, as each known mutation needs different sets of primer sets, their processing needs to be standardized. This results in such techniques requiring a comparatively long time for standardization. Nonsequencing molecular methods have another limitation of not detecting multiple mutations in a short region. Thus, any gene having multiple mutations needs an individual procedure for detecting mutations, making this process very complex and time-consuming. This process requires a large number of samples as well as appropriate positive and negative controls to confirm that the assays are working well. Moreover, some of the nonsequencing-based methods (e.g., ARMS-PCR) may end up in nonspecific signals due to the high DNA concentration. Thus, such samples may need to be diluted and restandardized for samples specific results analysis. Overall, the nonsequencing-based methods can be helpful in detecting limited genetic mutations that have been well correlated with a specific disease or phenotype. However, unlike NGS techniques, it does not support a personalized healthcare approach for individual patients, where all mutations specific to a disease can be simultaneously analyzed.

 » Emerging Sequencing-Based Emerging Molecular Modalities Top

The most prominent breakthrough of DNA sequencing came in 1977 which was Sanger Dideoxy synthesis. In 1980, the Maxam–Gilbert chemical cleavage method was also introduced by Maxam and Gilbert, which is based on the chemical modification of DNA and subsequent cleavage of the DNA backbone at sites adjacent to the modified nucleotides. The Sanger sequencing method has been the most preferred method of identifying alterations in small regions of the genes. Further, with the innovation of a better laser detection system and progress in computational hardware and software, more efficient methods have been developed. In 2005, Next-Generation Sequencing (NGS) technique was developed; since then, it has been used for various studies. In 2009, this technique was used for studying Human genome-specific mutations. In 2011, this technique was approved by FDA to be used for diagnosis in clinical setups. Till now, a large number of sequencing methods have been developed that provide extensive options as per user requirements [Table 4]. Some of the advanced NGS platforms can generate billions of reads per run and may analyze a large set of samples per run. Thus, NGS has evolved as one of the most advanced techniques for identifying genetic disorders in patients. Further, due to the association of many genetic alterations in myopathies and dystrophies, Sanger-Sequencing and NGS also seem to be suitable techniques in identifying such neuromuscular disorders [Figure 1]. Moreover, with the advancement in sequencing from single cells and from circulating nucleic acids, better methods for many neuromuscular disorders can be achieved in the future.
Figure 1: Workflow showing general strategies for diagnostic evaluation of myopathies and dystrophies (with red highlighted part showing the role of sequencing and/or NGS-based analysis approach)

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Table 4: Details of some next-generation sequencing platforms in order of maximum output range/run

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 » Conclusions Top

Early detection of myopathies and dystrophies can be an essential step that may lead to better health outcomes than treating them at a later stage. Moreover, screening such patients at an early stage, before any symptoms become noticeable, can also be a very effective technique. Developing novel methods using nonsequencing-based methods, including Tetra ARMS-PCR, Nested PCR, and RFLP, can be very helpful in the timely screening of such mutations across regions that are more susceptible to such mutilation. This study also values the importance of NGS and coincide with its central role in identifying and better-classifying myopathies and dystrophies in the future. However, we also highlight the importance and role of various screening methods that hold great potential in economically poor and developing countries. Although earlier screening holds a promising role in myopathies, the reliability of screening methods should be confirmed by scientists and medical investigators. Further, the importance of screening methods can benefit patients from starting treatment earlier rather than later. As many myopathies and dystrophies are associated with multiple genetic alterations, cases found positive during any single genetic alteration during initial screening should also be validated using a more reliable method for more accurate diagnosis. Alongside known benefits, screening may also notably cause harm to many patients who are given either a false positive test result or in such disorders where no effective treatment is available. Thus, potential participants involved in any such study should be provided all the necessary information to decide to participate in such screenings. Overall, we promote nonsequencing-based molecular methods for early-stage diagnosis and management of myopathies in developing countries and suggest the importance of emerging NGS-based methods in identifying new genetic players in neuromuscular disorders.

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Conflicts of interest

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 » References Top

Gomez-Vargas A, Baker SK. Molecular diagnosis of myopathies. Rheum Dis Clin North Am 2011;37:269-87.  Back to cited text no. 1
Cardamone M, Darras BT, Ryan MM. Inherited myopathies and muscular dystrophies. Semin Neurol 2008;28:250-9.  Back to cited text no. 2
M. King W, Kissel JT. Multidisciplinary approach to the management of myopathies. Contin Lifelong Learn Neurol 2013;19:1650-73.  Back to cited text no. 3
Latronico N, Rasulo FA. Presentation and management of ICU myopathy and neuropathy. Curr Opin Crit Care 2010;16:123-7.  Back to cited text no. 4
Pérez-López J, Selva-O'Callaghan A, Grau-Junyent JM, Gallego-Galindo L, Coll MJ, García-Morillo S, et al. Delayed diagnosis of late-onset Pompe disease in patients with myopathies of unknown origin and/or hyperCKemia. Mol Genet Metab 2015;114:580-3.  Back to cited text no. 5
Udd B, Krahe R. The myotonic dystrophies: Molecular, clinical, and therapeutic challenges. Lancet Neurol 2012;11:891-905.  Back to cited text no. 6
Sacconi S, Salviati L, Bourget I, Figarella D, Péréon Y, Lemmers R, et al. Diagnostic challenges in facioscapulohumeral muscular dystrophy. Neurology 2006;67:1464-6.  Back to cited text no. 7
Carrillo N, Malicdan MC, Huizing M. GNE myopathy: Etiology, diagnosis, and therapeutic challenges. Neurotherapeutics 2018;15:900-14.  Back to cited text no. 8
Béhin A, Salort-Campana E, Wahbi K, Richard P, Carlier RY, Carlier P, et al. Myofibrillar myopathies: State of the art, present and future challenges. Rev Neurol (Paris) 2015;171:715-29.  Back to cited text no. 9
Manie M. Meeting the challenges in the diagnosis of inflammatory myopathies. South African Med J 2015;105:1076.  Back to cited text no. 10
Nalini A, Nishino I, Gayathri N, Hayashi Y. GNE myopathy in India. Neurol India 2013;61:371.  Back to cited text no. 11
Zhu W, Mitsuhashi S, Yonekawa T, Noguchi S, Huei JCY, Nalini A, et al. Missing genetic variations in GNE myopathy: Rearrangement hotspots encompassing 5′UTR and founder allele. J Hum Genet 2017;62:159-66.  Back to cited text no. 12
Papadimas GK, Evilä A, Papadopoulos C, Kararizou E, Manta P, Udd B. GNE-myopathy in a Greek Romani family with unusual calf phenotype and protein aggregation pathology. J Neuromuscul Dis 2016;3:283-8.  Back to cited text no. 13
Argov Z, Mitrani Rosenbaum S. GNE myopathy: Two clusters with history and several founder mutations. J Neuromuscul Dis 2015;2:S73-6.  Back to cited text no. 14
Pogoryelova O, Cammish P, Skrinar A, Rao S, Lochmüller H, Kakis E. GNE myopathy worldwide epidemiology based on the patient self-reported registry. Neuromuscul Disord 2015;25:S281.  Back to cited text no. 15
Kimura E, Nakamura H, Hayashi YK, Mori-Yoshimura M, Shimuzu R, Komaki H, et al. Current status of dystrophinopathy patient registry in Japan: Remudy. Neuromuscul Disord 2013;23:776.  Back to cited text no. 16
Bhattacharya S, Khadilkar SV, Nalini A, Ganapathy A, Mannan AU, Majumder PP, et al. Mutation spectrum of GNE myopathy in the Indian sub-continent. J Neuromuscul Dis 2018;5:85-92.  Back to cited text no. 17
Lefter S, Hardiman O, Ryan AM. A population-based epidemiologic study of adult neuromuscular disease in the Republic of Ireland. Neurology 2017;88:304-13.  Back to cited text no. 18
Zatz M, Passos-Bueno MR, Vainzof M. Neuromuscular disorders: Genes, genetic counseling and therapeutic trials. Genet Mol Biol 2016;39:339-48.  Back to cited text no. 19
Khadilkar SV, Singh RK. Limb girdle muscular dystrophies in India. Neurol India 2008;56:281-8.  Back to cited text no. 20
[PUBMED]  [Full text]  
Cherrallah A, Benhassine T, Nouioua S, Makri S, Chaouch M, Tazir M, et al. Intragenic deletion patterns of dystrophin gene in Duchenne and Becker muscular dystrophy patients from Algeria. Genes Genomics 2014;36:17-24.  Back to cited text no. 21
Lee YS. Muscle diseases in Singapore. Pathology 1986;18:35-40.  Back to cited text no. 22
Theadom A, Rodrigues M, Roxburgh R, Balalla S, Higgins C, Bhattacharjee R, et al. Prevalence of muscular dystrophies: A systematic literature review. Neuroepidemiology 2014;43:259-68.  Back to cited text no. 23
Albuquerque MAV. Limb-girdle muscular dystrophy in Brazilian children: Clinical, histological and molecular characterization. Arq Neuropsiquiatr 2014;72:481.  Back to cited text no. 24
de Almeida PAD, Machado-Costa MC, Manzoli GN, Ferreira LS, Rodrigues MCS, Bueno LSM, et al. Genetic profile of Brazilian patients with dystrophinopathies. Clin Genet 2017;92:199-203.  Back to cited text no. 25
Celeste FV, Vilboux T, Ciccone C, de Dios JK, Malicdan MC, Leoyklang P, et al. Mutation update for GNE gene variants associated with GNE myopathy. Hum Mutat 2014;35:915-26.  Back to cited text no. 26
Pogoryelova O, Wilson IJ, Mansbach H, Argov Z, Nishino I, Lochmüller H. GNE genotype explains 20% of phenotypic variability in GNE myopathy. Neurol Genet 2019;5:e308. doi: 10.1212/NXG.0000000000000308.  Back to cited text no. 27
Selva-O'Callaghan A, Gil-Vila A, Simó-Perdigó M, Trallero-Araguás E, Alvarado-Cárdenas M, Pinal-Fernandez I. PET Scan: Nuclear medicine imaging in myositis. Curr Rheumatol Rep 2019;21:64.  Back to cited text no. 28
Nishino I, Carrillo-carrasco N, Argov Z, Diseases N. GNE Myopathy: Current update and future therapy. Monatsschr Kinderheilkd 1988;136:403-12.  Back to cited text no. 29
Burr ML, Roos JC, ístör AJK. Metabolic myopathies: A guide and update for clinicians. Curr Opin Rheumatol 2008;20:639-47.  Back to cited text no. 30
Massalska D, Zimowski JG, Bijok J, Kucińska-Chahwan A, Łusakowska A, Jakiel G, et al. Prenatal diagnosis of congenital myopathies and muscular dystrophies. Clin Genet 2016;90:199-210.  Back to cited text no. 31
Access O. Chapter 6_Hereditary Myopathies. Long-Haul Travel Motiv by Int Tour to Penang 2018;i: 13.  Back to cited text no. 32
Castro C, Gourley M. Diagnosis and treatment of inflammatory myopathy: Issues and management. Ther Adv Musculoskelet Dis 2012;4:111-20.  Back to cited text no. 33
Tarnopolsky M. Metabolic myopathies. In: International Encyclopedia of Public Health. 2016.  Back to cited text no. 34
Gilbreath HR, Castro D, Iannaccone ST. Congenital myopathies and muscular dystrophies. Neurol Clin 2014;32:689-703.  Back to cited text no. 35
Van Adel BA, Tarnopolsky MA. Metabolic myopathies: Update 2009. J Clin Neuromuscul Dis 2009;10:97-121.  Back to cited text no. 36
Shieh PB. Muscular Dystrophies and other genetic myopathies. Neurol Clin 2013;31:1009-29.  Back to cited text no. 37
Quan D. Muscular dystrophies and neurologic diseases that present as myopathy. Rheum Dis Clin North Am 2011;37:233-44.  Back to cited text no. 38
Bodhini D, Radha V, Dhar M, Narayani N, Mohan V, Ye S, et al. An efficient procedure for genotyping single nucleotide polymorphisms. Metabolism 2007;56:1174-8.  Back to cited text no. 39
Fanin M, Fulizio L, Nascimbeni AC, Spinazzi M, Piluso G, Ventriglia VM, et al. Molecular diagnosis in LGMD2A: Mutation analysis of protein testing? Hum Mutat 2004;24:52-62.  Back to cited text no. 40
Yang L, Ijaz I, Cheng J, Wei C, Tan X, Khan MA, et al. Evaluation of amplification refractory mutation system (ARMS) technique for quick and accurate prenatal gene diagnosis of CHM variant in choroideremia. Appl Clin Genet 2018;11:1-8.  Back to cited text no. 41
Bai RK, Wong LJC. Detection and quantification of heteroplasmic mutant mitochondrial DNA by real-time amplification refractory mutation system quantitative PCR analysis: A single-step approach. Clin Chem 2004;50:996-1001.  Back to cited text no. 42
Attali R, Aharoni S, Treves S, Rokach O, Becker Cohen M, Fellig Y, et al. Variable myopathic presentation in a single family with novel skeletal RYR1 mutation. PLoS One 2013;8:e69296.  Back to cited text no. 43
Huang W, Zhang C, Xie YM, Chen SL, Jiao ZX, Zhou C, et al. Single cell analysis of some deletion in dystrophin gene exons and gender determination by 3-plex nested PCR. Chinese J Med Genet 2004;21:389-91.  Back to cited text no. 44
Malcov M, Ben-Yosef D, Schwartz T, Mey-Raz N, Azem F, Lessing JB, et al. Preimplantation genetic diagnosis (PGD) for Duchenne muscular dystrophy (DMD) by triplex-nested PCR. Prenat Diagn 2005;25:1200-5.  Back to cited text no. 45
Fardeau M, Braun S, Romero NB, Hogrel JY, Rouche A, Ortega V, et al. About a phase I gene therapy clinical trial with a full-length dystrophin gene-plasmid in Duchenne/Becker muscular dystrophy. J la Soc Biol 2005;199:29-32.  Back to cited text no. 46
Gergely P, Blazsek A, Dankó K, Ponyi A, Poór G. Detection of TT virus in patients with idiopathic inflammatory myopathies. Ann N Y Acad Sci 2005;1050:304-13.  Back to cited text no. 47
Joshi PR, Hauburger A, Kley R, Claeys KG, Schneider I, Kress W, et al. Mitochondrial abnormalities in myofibrillar myopathies. Clin Neuropathol 2014;33:134-42.  Back to cited text no. 48
Scuderi C, Borgione E, Castello F, Giudice M Lo, Fichera M, Elia M, et al. Coexistence of mitochondrial and nuclear DNA mutations in a woman with mitochondrial encephalomyopathy and double cortex. Mitochondrion 2010;10:548-54.  Back to cited text no. 49
Shojasaffar B, Moradin N, Kahrizi K, Cobo AM, Najmabadi H. CTG Expansion and haplotype analysis in DM1 gene in healthy Iranian population. Can J Neurol Sci 2008;35:216-9.  Back to cited text no. 50
Rubio JC, Garcia-Consuegra I, Nogales-Gadea G, Blazquez A, Cabello A, Lucia A, et al. A proposed molecular diagnostic flowchart for myophosphorylase deficiency (McArdle disease) in blood samples from Spanish patients. Hum Mutat 2007;28:203-4.  Back to cited text no. 51
Cardaioli E, Pozzo P Da, Radi E, Dotti MT, Federico A. A novel heteroplasmic tRNA Leu (CUN) mtDNA point mutation associated with chronic progressive external ophthalmoplegia. Biochem Biophys Res Commun 2005;327:675-8.  Back to cited text no. 52
Malayeri FA, Panjehpour M, Movahedian A, Ghaffarpour M, Zamani GR, Tabrizi MH, et al. Detection of duchenne/becker muscular dystrophy carriers in a group of Iranian families by linkage analysis. Acta Med Iran 2011;49:142-8.  Back to cited text no. 53
Wojcik KA, Synowiec E, Kaminska A, Izdebska J, Polakowski P, Pawlowska E, et al. Polymorphism of the APEX nuclease 1 gene in keratoconus and Fuchs endothelial corneal dystrophy. Cell Mol Biol Lett 2015;20:48-65.  Back to cited text no. 54
Foja S, Hoffmann K, Auw-Haedrich C, Reinhard T, Rupprecht A, Gruenauer-Kloevekorn C. Identification of two novel mutations in the cornea-specific TGFBI gene causing unique phenotypes in patients with corneal dystrophies. Int Ophthalmol 2016;36:867-73.  Back to cited text no. 55
Tallapaka K, Ranganath P, Ramachandran A, Uppin MS, Perala S, Aggarwal S, et al. Molecular and histopathological characterization of patients presenting with the duchenne muscular dystrophy phenotype in a tertiary care center in Southern India. Indian Pediatr 2019;56:556-9.  Back to cited text no. 56
Polavarapu K, Preethish-Kumar V, Sekar D, Vengalil S, Nashi S, Mahajan NP, et al. 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. J Neurol 2019;266:2177-85.  Back to cited text no. 57
Zhao HH, Sun XP, Shi MC, Yi YX, Cheng H, Wang XX, et al. Molecular analysis-based genetic characterization of a cohort of patients with duchenne and becker muscular dystrophy in Eastern China. Chin Med J (Engl) 2018;131:770-5.  Back to cited text no. 58
Kong X, Zhong X, Liu L, Cui S, Yang Y, Kong L. Genetic analysis of 1051 Chinese families with Duchenne/Becker muscular dystrophy. BMC Med Genet 2019;20:139.  Back to cited text no. 59
Thakur N, Abeysekera G, Wanigasinghe J, Dissanayake VHW. The spectrum of deletions and duplications in the dystrophin (DMD) gene in a cohort of patients with Duchenne muscular dystrophy in Sri Lanka. Neurol India 2019;67:714-5.  Back to cited text no. 60
[PUBMED]  [Full text]  
Mohammed F, Elshafey A, Al-balool H, Alaboud H, Ali MA Ben, Baqer A, et al. Mutation spectrum analysis of Duchenne/Becker muscular dystrophy in 68 families in Kuwait: The era of personalized medicine. PLoS One 2018;13. doi: 10.1371/journal.pone. 0197205.  Back to cited text no. 61
Kumari P, Joshi D, Shamal SN, Singh R. Study of dystrophinopathy in eastern Uttar Pradesh population of India. J Pediatr Neurosci 2018;13:182-8.  Back to cited text no. 62
[PUBMED]  [Full text]  
Li Y, Liu Z, OuYang S, Zhu Y, Wang L, Wu J. Distribution of dystrophin gene deletions in a Chinese population. J Int Med Res 2016;44:99-108.  Back to cited text no. 63
Sedghi M, Nouri N, Fazel-Najafabadi E, Salehi M, Hosseinzadeh M, Behnam M, et al. Evaluation of multiplex ligation-dependent probe amplification analysis versus multiplex polymerase chain reaction assays in the detection of dystrophin gene rearrangements in an Iranian population subset. Adv Biomed Res 2014;3:72.  Back to cited text no. 64
[PUBMED]  [Full text]  
Syu JR, Wang CC, Jong YJ, Wu SM. Genotyping of exons 1 to 20 in Duchenne muscular dystrophy by universal multiplex PCR and short-end capillary electrophoresis. Electrophoresis 2014;35:3387-94.  Back to cited text no. 65


  [Figure 1]

  [Table 1], [Table 2], [Table 3], [Table 4]


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