Search Our Scientific Publications & Authors

Indian J Pathol Microbiol 2022 May;65(Supplement):S259-S270

Department of Medical Genetics, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad, Telangana, India.

Muscular dystrophies are a clinically and genetically heterogeneous group of disorders involving the skeletal muscles. They have a progressive clinical course and are characterized by muscle fiber degeneration. Congenital muscular dystrophies (CMD) include dystroglycanopathies, merosin-deficient CMD, collagen VI-deficient CMD, SELENON-related rigid spine muscular dystrophy, and LMNA-related CMD. Read More

Acta Myol 2022 Mar 31;41(1):1-14. Epub 2022 Mar 31.

Department of Medical Genetics, Faculty of Medicine, Ain Shams University, Cairo, Egypt.

Duchenne muscular dystrophy (DMD) is a progressive genetic muscle disease. Quantitative muscle ultrasound (US), muscle MRI, and functional tools are important to delineate characteristics of muscle involvement. We aimed to establish correlations between clinical/functional and above-named imaging tools respecting their diagnostic and prognostic role in DMD children. Read More

Muscle Nerve 2022 05 4;65(5):521-530. Epub 2022 Mar 4.

Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.

Introduction/aims: Serum cardiac troponin I (cTnI), its relation to cardiomyopathy, and the contribution of the ACTN3 genotype to serum levels of cTnI in Duchenne and Becker muscular dystrophy (DMD and BMD, respectively) remain unknown. In this study we aimed to reveal the characteristics of cTnI, assess whether cTnI is a biomarker for cardiomyopathy in these dystrophinopathies, and evaluate the contribution of the ACTN3 genotype to the serum levels of cTnI in DMD patients.

Methods: Serum cTnI values obtained from 127 DMD and 47 BMD patients were analyzed retrospectively. Read More

Cell Mol Life Sci 2022 Jan 30;79(2):109. Epub 2022 Jan 30.

Department of Pathology and Applied Neurobiology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, 465 Kajii-cho, Kawaramachi Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.

Duchenne muscular dystrophy (DMD), the most severe form of dystrophinopathies, is a fatal X-linked recessive neuromuscular disorder characterized by progressive muscle degeneration and various extents of intellectual disabilities. Physiological and pathological roles of the responsible gene, dystrophin, in the brain remain elusive due to the presence of multiple dystrophin products, mainly full-length dystrophin, Dp427, and the short product, Dp71. In this study, we generated a Dp71-specific hemagglutinin (HA) peptide tag-insertion mice to enable specific detection of intrinsic Dp71 expression by anti-HA-tag antibodies. Read More

J Cachexia Sarcopenia Muscle 2022 Apr 26;13(2):1360-1372. Epub 2022 Jan 26.

Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health, London, UK.

Background: Duchenne muscular dystrophy (DMD) is caused by DMD mutations leading to dystrophin loss. Full-length Dp427 is the primary dystrophin isoform expressed in muscle and is also expressed in the central nervous system (CNS). Two shorter isoforms, Dp140 and Dp71, are highly expressed in the CNS. Read More

Neuromuscul Disord 2022 02 3;32(2):159-165. Epub 2021 Nov 3.

Kempenhaeghe Centre for Neurological Learning Disabilities, Heeze, Netherlands; Maastricht University, School for Mental Health and Neuroscience, Maastricht, Netherlands; Duchenne Center Netherlands.

The primary aim of this study was to describe the psychometric properties of an adult revision of the 28 item Personal Adjustment and Role Skills Scale (PARS-III). This scale was originally developed to assess psychosocial adjustment in children 4-18 years of age and has been applied in boys with Duchenne muscular dystrophy (DMD) and was found to be reliable and valid. Within the context of a longer lifespan in dystrophinopathies there is a growing need to assess psychosocial adjustment in an adult population. Read More

Int J Mol Sci 2021 Dec 22;23(1). Epub 2021 Dec 22.

Unidade de Genética Molecular, Centro de Genética Médica Doutor Jacinto Magalhães, Centro Hospitalar Universitário do Porto (CHUPorto), 4099-028 Porto, Portugal.

While in most patients the identification of genetic alterations causing dystrophinopathies is a relatively straightforward task, a significant number require genomic and transcriptomic approaches that go beyond a routine diagnostic set-up. In this work, we present a Becker Muscular Dystrophy patient with elevated creatinine kinase levels, progressive muscle weakness, mild intellectual disability and a muscle biopsy showing dystrophic features and irregular dystrophin labelling. Routine molecular techniques (Southern-blot analysis, multiplex PCR, MLPA and genomic DNA sequencing) failed to detect a defect in the gene. Read More

Front Neurol 2021 7;12:718396. Epub 2021 Dec 7.

Department of Biochemistry and Molecular Biology, University of Bucharest, Bucharest, Romania.

Duchenne and Becker muscular dystrophy are X-linked recessive inherited disorders characterized by progressive weakness due to skeletal muscle degeneration. Different mutations in the gene, which encodes for dystrophin protein, are responsible for these disorders. The aim of our study was to investigate the relationship between type, size, and location of the mutation that occurs in the gene and their effect on dystrophin protein expression in a cohort of 40 male dystrophinopathy patients and nine females, possible carriers. Read More

Int J Mol Sci 2021 Dec 2;22(23). Epub 2021 Dec 2.

Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2H7, Canada.

Duchenne muscular dystrophy (DMD) is a lethal X-linked recessive disorder caused by mutations in the gene and the subsequent lack of dystrophin protein. Recently, phosphorodiamidate morpholino oligomer (PMO)-antisense oligonucleotides (ASOs) targeting exon 51 or 53 to reestablish the reading frame have received regulatory approval as commercially available drugs. However, their applicability and efficacy remain limited to particular patients. Read More

J Neuromuscul Dis 2022 ;9(1):171-178

Department of Neurology, School of Medicine and Dentistry, University of Rochester Medical Center, Rochester, USA.

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) phenotypes are used to describe disease progression in affected individuals. However, considerable heterogeneity has been observed across and within these two phenotypes, suggesting a spectrum of severity rather than distinct conditions. Characterizing the phenotypes and subphenotypes aids researchers in the design of clinical studies and clinicians in providing anticipatory guidance to affected individuals and their families. Read More

Hum Mol Genet 2022 May;31(9):1417-1429

School of Medicine, Western Sydney University, Sydney, NSW 2560, Australia.

The common null polymorphism (R577X) in the ACTN3 gene is present in over 1.5 billion people worldwide and results in the absence of the protein α-actinin-3 from the Z-discs of fast-twitch skeletal muscle fibres. We have previously reported that this polymorphism is a modifier of dystrophin-deficient Duchenne Muscular Dystrophy. Read More

Neuromuscul Disord 2021 10;31(10):988-997

John Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle, UK. Electronic address:

The differential diagnosis of genetic muscle disease has become increasingly difficult due to the rapid progress in genetic medicine in recent years. Where classifications based on the clinical picture were attributed to one gene only a few years ago, today we know that a variety of clinical presentations can result from the same mutation and, conversely, various genes are associated with a similar phenotype. A significant consideration in assessing a patient with muscle weakness is the presence or absence of intellectual disability, thus narrowing the differential diagnostic approach in any child with an as yet undiagnosed muscle disease. Read More

Diagnostics (Basel) 2021 Oct 15;11(10). Epub 2021 Oct 15.

CEINGE-Biotecnologie Avanzate s.c.ar.l., 80145 Naples, Italy.

Duchenne/Becker muscular dystrophy (DMD/BMD) is an X-linked neuromuscular disease due to pathogenic sequence variations in the dystrophin ( gene, one of the largest human genes. More than 70% of gene defects result from genomic rearrangements principally leading to large deletions, while the remaining are small nucleotide variants, including nonsense and missense variants, small insertions/deletions or splicing alterations. Considering the large size of the gene and the wide mutational spectrum, the comprehensive molecular diagnosis of DMD/BMD is complex and may require several laboratory methods, thus increasing the time and costs of the analysis. Read More

J Clin Med 2021 Sep 24;10(19). Epub 2021 Sep 24.

Basic Medical Sciences, Neurosciences, and Sensory Organs Department, University of Bari "Aldo Moro", 70124 Bari, Italy.

A diagnosis of autism spectrum disorder is reported in up to 19% of dystrophinopathies. However, over the last ten years, only a few papers have been published on this topic. Therefore, further studies are required to analyze this association in depth and ultimately to understand the role of the brain dystrophin isoform in the pathogenesis of ASD and other neurodevelopmental disorders. Read More

Appl Clin Genet 2021 1;14:399-408. Epub 2021 Oct 1.

Center for Research in Genetics and Genomics - CIGGUR, GENIUROS Research Group, School of Medicine and Health Sciences, Universidad Del Rosario, Bogotá, DC, Colombia.

Background: Duchenne and Becker muscular dystrophies (DMD/BMD) are the most common human dystrophinopathies with recessive X-linked inheritance. Dystrophin gene deletions and duplications are the most common mutations, followed by point mutations. The aim of this study is to characterize the mutational profile of the dystrophin gene in Colombian patients with DMD/BMD. Read More

Folia Neuropathol 2021 ;59(3):276-283

Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Ciudad de México, México.

Muscular dystrophies are a group of well-defined genetic disorders characterized by the variable distribution of muscle wasting and progressive weakness. The diagnosis and treatment of these diseases remain challenging due to genetic heterogeneity and clinical overlapping. Herein, we describe our 10 years' experience with the diagnosis and management of muscular dystrophy patients. Read More

Pflugers Arch 2021 12 22;473(12):1813-1839. Epub 2021 Sep 22.

Institute of Physiology, University of Bonn, 53115, Bonn, Germany.

Duchenne muscular dystrophy is a highly progressive muscle wasting disorder due to primary abnormalities in one of the largest genes in the human genome, the DMD gene, which encodes various tissue-specific isoforms of the protein dystrophin. Although dystrophinopathies are classified as primary neuromuscular disorders, the body-wide abnormalities that are associated with this disorder and the occurrence of organ crosstalk suggest that a multi-systems pathophysiological view should be taken for a better overall understanding of the complex aetiology of X-linked muscular dystrophy. This article reviews the molecular and cellular effects of deficiency in dystrophin isoforms in relation to voluntary striated muscles, the cardio-respiratory system, the kidney, the liver, the gastrointestinal tract, the nervous system and the immune system. Read More

Int J Mol Sci 2021 Aug 19;22(16). Epub 2021 Aug 19.

Unit of Vascular Biology and Regenerative Medicine, Centro Cardiologico Monzino-IRCCS, 20138 Milan, Italy.

Despite major progress in treating skeletal muscle disease associated with dystrophinopathies, cardiomyopathy is emerging as a major cause of death in people carrying dystrophin gene mutations that remain without a targeted cure even with new treatment directions and advances in modelling abilities. The reasons for the stunted progress in ameliorating dystrophin-associated cardiomyopathy (DAC) can be explained by the difficulties in detecting pathophysiological mechanisms which can also be efficiently targeted within the heart in the widest patient population. New perspectives are clearly required to effectively address the unanswered questions concerning the identification of authentic and effectual readouts of DAC occurrence and severity. Read More

Muscle Nerve 2021 11 25;64(5):576-584. Epub 2021 Aug 25.

C.J. Gorter Center for High Field MRI, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.

Introduction/aims: Duchenne and Becker muscular dystrophies (DMD and BMD, respectively) are characterized by fat replacement of different skeletal muscles in a specific temporal order. Given the structural role of dystrophin in skeletal muscle mechanics, muscle architecture could be important in the progressive pathophysiology of muscle degeneration. Therefore, the aim of this study was to assess the role of muscle architecture in the progression of fat replacement in DMD and BMD. Read More

Acta Myol 2021 Jun 30;40(2):93-100. Epub 2021 Jun 30.

Departamento de Ciências Básicas da Saúde and Laboratório de Biologia Celular, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil.

Pathogenic germline variants in gene, which encodes the well-known cytoskeletal protein named dystrophin, are associated with a wide range of dystrophinopathies disorders, such as Duchenne muscular dystrophy (DMD, severe form), Becker muscular dystrophy (BMD, mild form) and intermediate muscular dystrophy (IMD). Muscle biopsy, immunohistochemistry, molecular (multiplex ligation-dependent probe amplification (MLPA)/next-generation sequencing (NGS) and Sanger methods) and in silico analyses were performed in order to identify alterations in gene and protein in a patient with a clinical manifestation and with high creatine kinase levels. Herein, we described a previously unreported intronic variant in and reduced dystrophin staining in the muscle biopsy. Read More

Neuromuscul Disord 2021 08 2;31(8):788-797. Epub 2021 Jun 2.

Department of Neurology, School of Medical Sciences, University of Campinas (UNICAMP), 126. Cidade Universitaria "Zeferino Vaz", Campinas, SP 13083-887, Brazil. Electronic address:

Dystrophinopathies are a group of X-linked neuromuscular disorders that result from pathogenic variants in the DMD gene. Their pathophysiological substrate is the defective expression of dystrophin in many tissues. While patients from the same pedigree usually present similar dystrophin expression and clinical course, the extent of cardiac and skeletal muscle involvement may not correlate in the same individual. Read More

Cardiovasc Res 2021 Jul 12. Epub 2021 Jul 12.

Fondazione Policlinico Universitario A. Gemelli IRCCS, Department of Cardiovascular Sciences, Rome, Italy.

Alterations in the DMD gene, which codes for the protein dystrophin, cause forms of dystrophinopathies such as Duchenne muscular dystrophy, an X-linked disease. Cardiomyopathy linked to DMD mutations is becoming the leading cause of death in patients with dystrophinopathy. Since phenotypic pathophysiological mechanisms are not fully understood, the improvement and development of new disease models, considering their relative advantages and disadvantages, is essential. Read More

Ann Noninvasive Electrocardiol 2021 11 11;26(6):e12876. Epub 2021 Jul 11.

Division of Cardiology.

Introduction: Heart disease remains a leading cause of mortality in patients with muscular dystrophy (MD), and cardiac assessment by standard imaging modalities is challenging due to the prominence of physical limitations.

Methods: In this prospective cohort study of 169 MD patients and 34 negative control patients, we demonstrate the clinical utility of a 12-lead electrocardiogram (ECG) as an effective modality for the assessment of cardiac status in patients with MD. We assessed the utility of conventional criteria for electrocardiogram-indicated left ventricular hypertrophy (ECG-LVH) as well as ECG morphologies. Read More

Eur J Heart Fail 2021 08 6;23(8):1287-1289. Epub 2021 Jul 6.

Cardiothoracovascular Department, Center for Diagnosis and Management of Cardiomyopathies, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), University of Trieste, Trieste, Italy.

Front Neurol 2021 11;12:659922. Epub 2021 Jun 11.

Neuromuscular Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Departament de Medicina. Universitat Autònoma de Barcelona, Barcelona, Spain.

Duchenne (DMD) and Becker (BMD) muscular dystrophy are X-linked muscular disorders produced by mutations in the DMD gene which encodes the protein dystrophin. Both diseases are characterized by progressive involvement of skeletal, cardiac, and respiratory muscles. As new treatment strategies become available, reliable biomarkers and outcome measures that can monitor disease progression are needed for clinical trials. Read More

Front Pharmacol 2021 3;12:648390. Epub 2021 Jun 3.

Laboratorio de Distrofinopatías, Cátedra de Genética, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.

Dystrophinopathies cover a spectrum of rare progressive X-linked muscle diseases, arising from mutations. They are among the most common pediatric muscular dystrophies, being Duchenne muscular dystrophy (DMD) the most severe form. Despite the fact that there is still no cure for these serious diseases, unprecedented advances are being made for the development of therapies for DMD. Read More

Muscle Nerve 2021 09 16;64(3):255-269. Epub 2021 Jun 16.

Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.

Despite recent advances in the understanding of inherited muscle and neuromuscular junction diseases, as well as the advent of a wide range of genetic tests, patients continue to face delays in diagnosis of sometimes treatable disorders. These guidelines outline an approach to genetic testing in such disorders. Initially, a patient's phenotype is evaluated to identify myopathies requiring directed testing, including myotonic dystrophies, facioscapulohumeral muscular dystrophy, oculopharyngeal muscular dystrophy, mitochondrial myopathies, dystrophinopathies, and oculopharyngodistal myopathy. Read More

Orphanet J Rare Dis 2021 Jun 2;16(1):252. Epub 2021 Jun 2.

Research Institute of Neuromuscular and Neurodegenerative Diseases and Department of Neurology, Qilu Hospital, Shandong University, Jinan, Shandong, China.

Neurol Genet 2021 Feb 29;7(1):e554. Epub 2021 Jan 29.

Kids Neuroscience Centre (L.B.W., S.J.B., A.B., F.J.E., H.J., S.A.S., G.L.O., E.C.O., N.F.C., K.J.J., S.T.C.), Kids Research Institute, The Children's Hospital at Westmead, New South Wales, Australia; Discipline of Child and Adolescent Health (L.B.W., S.J.B., A.B., F.J.E., S.A.S., G.L.O., E.C.O., N.F.C., K.J.J., S.T.C.), Faculty of Medicine and Health, The University of Sydney, Westmead, New South Wales, Australia; Analytic and Translational Genetics Unit (B.B.C., J.L.M., T.T., E.V., D.G.M., M.L.), Massachusetts General Hospital, Boston; Medical and Population Genetics (B.B.C., J.L.M., T.T., E.V., B.W., S.S., D.G.M., M.L.), and Center for Mendelian Genomics (B.B.C., J.L.M., E.V., B.W., S.S., D.G.M., M.L.), Broad Institute of MIT & Harvard, Cambridge, MA; Functional Neuromics (F.J.E., S.T.C.), Children's Medical Research Institute, Westmead, New South Wales, Australia; Murdoch Children's Research Institute (S.S.), Parkville, Victoria, Australia; Department of Diagnostic Genomics (M.R.D., F.F., R.G.), PathWest Laboratory Medicine WA, Nedlands, Australia; Department of Clinical Genetics (S.A.S., A.M., K.J.J.), Children's Hospital at Westmead, New South Wales, Australia; Department of Genetic Medicine (M.C.T.), Westmead Hospital, New South Wales, Australia; Discipline of Genomic Medicine (M.C.T., A.M.), Sydney Medical School, The University of Sydney, New South Wales, Australia; Centre for Clinical Genetics (D.R.M.), Sydney Children's Hospital, Randwick, New South Wales, Australia; School of Women's and Children's Health (D.R.M., M.A.F.), UNSW Medicine, UNSW Sydney, Australia; Department of Neurology (M.A.F., H.S.), Sydney Children's Hospital, Randwick, New South Wales, Australia; Department of Clinical Genetics (A.M.), Nepean Hospital, Sydney, Australia; Genetic Health Service NZ (K.N.), Wellington, New Zealand; Neurology Laboratory (M.-X.W.), Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia; Central Clinical School (M.-X.W.), Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia; Anatomic Pathology (A.C., C.C., N.G., S.A.), The Children's Hospital at Westmead, New South Wales, Australia; Anatomic Pathologist (D.N.K.), Department of Pathology and Molecular Medicine, University of Otago, Wellington, New Zealand; and Harvard Medical School (D.G.M.), Boston, MA.

Objective: To describe the diagnostic utility of whole-genome sequencing and RNA studies in boys with suspected dystrophinopathy, for whom multiplex ligation-dependent probe amplification and exomic parallel sequencing failed to yield a genetic diagnosis, and to use remnant normal splicing in 3 families to define critical levels of wild-type dystrophin bridging clinical spectrums of Duchenne to myalgia.

Methods: Exome, genome, and/or muscle RNA sequencing was performed for 7 males with elevated creatine kinase. PCR of muscle-derived complementary DNA (cDNA) studied consequences for premessenger RNA (pre-mRNA) splicing. Read More