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Acta Myol 2020 Mar 1;39(1):24-28. Epub 2020 Mar 1.

Neuromuscular Disease Unit, Neurology Department, Coimbra University and Hospital Centre, Coimbra, Portugal.

Myopathies caused by gene mutations are clinically and pathologically heterogeneous and, until recently, difficult to diagnose. The availability of NGS panels for hereditary neuromuscular diseases changed our insight regarding their frequency and allowed a better perception of the different phenotypes and morphological abnormalities associated. We present a male Portuguese patient with the classical phenotype of Laing early-onset distal myopathy (MPD1) beginning at 6 years of age, very slowly progressive, and with a mild to moderate impact on daily life by the age of 56. Read More

Eur J Hum Genet 2020 Jun 22. Epub 2020 Jun 22.

Signature Research Program in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School, Singapore, 169857, Singapore.

Major Facilitator Superfamily Domain containing 2a (MFSD2A) is an essential endothelial lipid transporter at the blood-brain barrier. Biallelic variants affecting function in MFSD2A cause autosomal recessive primary microcephaly 15 (MCPH15, OMIM# 616486). We sought to expand our knowledge of the phenotypic spectrum of MCPH15 and demonstrate the underlying mechanism of inactivation of the MFSD2A transporter. Read More

Zhongguo Dang Dai Er Ke Za Zhi 2020 Jun;22(6):608-613

Department of Pediatrics, First Affiliated Hospital, Jinan University, Guangzhou 510630, China.

Biallelic pathogenic mutations of the LAMA2 gene result in congenital muscular dystrophy type 1A (CMD1A). The patient in this study was a boy aged 19 months, with the clinical manifestations of motor development delay and increases in the serum levels of creatine kinase, aminotransferases, and lactate dehydrogenase. Genetic analysis showed that the patient had compound heterozygous mutations in the LAMA2 gene, among which c. Read More

Arch Med Sci 2020 18;16(4):715-726. Epub 2019 Nov 18.

Laboratory of Gastroimmunology, Department of Immunology and Infectious Biology, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.

Ankyrins are adaptor molecules that in eukaryotic cells form complexes with ion channel proteins, cell adhesion and signalling molecules and components of the cytoskeleton. They play a pivotal role as scaffolding proteins, in the structural anchoring to the muscle membrane, in muscle development, neurogenesis and synapse formation. Dysfunction of ankyrins is implicated in numerous diseases such as hereditary spherocytosis, neurodegeneration of Purkinje cells, cardiac arrhythmia, Brugada syndrome, bipolar disorders and schizophrenia, congenital myopathies and congenital heart disease as well as cancers. Read More

Therap Adv Gastroenterol 2020 26;13:1756284820923220. Epub 2020 May 26.

Digestive Endoscopy and Surgical Unit, Ospedale Pediatrico Bambino Gesù, Roma, Italy.

Background: Since the esophagus has no redundancy, congenital and acquired esophageal diseases often require esophageal substitution, with complicated surgery and intestinal or gastric transposition. Peri-and-post-operative complications are frequent, with major problems related to the food transit and reflux. During the last years tissue engineering products became an interesting therapeutic alternative for esophageal replacement, since they could mimic the organ structure and potentially help to restore the native functions and physiology. Read More

Front Mol Neurosci 2020 25;13:69. Epub 2020 May 25.

Felsenstein Medical Research Center (FMRC), Tel-Aviv University, Tel-Aviv, Israel.

Muscle stem cells (MuSCs), known as satellite cells (SCs) have an incredible ability to regenerate, which enables the maintenance and growth of muscle tissue. In response to damaging stimuli, SCs are activated, proliferate, differentiate, and fuse to repair or generate a new muscle fiber. However, dystrophic muscles are characterized by poor muscle regeneration along with chronic inflammation and fibrosis. Read More

Hum Mutat 2020 Jun 9. Epub 2020 Jun 9.

Department of Pediatric Neurology, Developmental Neurology and Social Pediatrics, University of Essen, Germany.

Filamin C (encoded by the FLNC gene) is a large actin-cross-linking protein involved in shaping the actin cytoskeleton in response to signaling events both at the sarcolemma and at myofibrillar Z-discs of cross-striated muscle cells. Multiple mutations in FLNC are associated with myofibrillar myopathies of autosomal dominant inheritance. Here, we describe for the first time a boy with congenital onset of generalized muscular hypotonia and muscular weakness, delayed motor development but no cardiac involvement associated with a homozygous FLNC mutation c. Read More

Mol Ther Methods Clin Dev 2020 Jun 4;17:1178-1189. Epub 2020 May 4.

Dynacure, Illkirch, France.

Myotubular myopathy, also called X-linked centronuclear myopathy (XL-CNM), is a severe congenital disease targeted for therapeutic trials. To date, biomarkers to monitor disease progression and therapy efficacy are lacking. The mouse is a faithful model for XL-CNM, due to myotubularin 1 () loss-of-function mutations. Read More

J Biol Chem 2020 Jun 4. Epub 2020 Jun 4.

Basel University Hospital, Switzerland.

Mutations in the ryanodine receptor 1 (RYR1) gene are associated with several human congenital myopathies including the dominantly inherited central core disease and exercise- induced rhabdomyolysis and the more severe recessive phenotypes including multiminicore disease, centronuclear myopathy and congenital fiber type disproportion. Within the latter group, those carrying a hypomorphic mutation in one allele and a missense mutation in the other are the most severely affected. Because of nonsense-mediated decay, most hypomorphic alleles are not expressed, resulting in homozygous expression of the missense mutation allele. Read More

Intractable Rare Dis Res 2020 May;9(2):104-108

Genetic Counseling Center, Shiraz Welfare Organization, Shiraz, Iran.

Dystroglycan (DG) is a major cell membrane glycoprotein, which is encoded by the gene. α-DG is one of DG subunits, belongs to O-mannosylated protein of mammals and was identified in brain, peripheral nerves and muscle. Dystroglycanopathies are a group of heterogeneous congenital muscular dystrophies, which can result from defective α-DG mannosylation. Read More

Eur Radiol Exp 2020 Jun 3;4(1):33. Epub 2020 Jun 3.

Medical Molecular Imaging Group, Vall d'Hebron Research Institute (VHIR), CIBER-BBN, CIBBIM-Nanomedicine, ISCIII, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona (UAB), Passeig de la Vall d'Hebron 119-129, 08035, Barcelona, Spain.

Background: Skeletal muscle injury characterisation during healing supports trauma prognosis. Given the potential interest of computed tomography (CT) in muscle diseases and lack of in vivo CT methodology to image skeletal muscle wound healing, we tracked skeletal muscle injury recovery using in vivo micro-CT in a rat model to obtain a predictive model.

Methods: Skeletal muscle injury was performed in 23 rats. Read More

Int J Mol Sci 2020 May 24;21(10). Epub 2020 May 24.

st Department of Neurology, Eginition Hospital, Medical School, National and Kapodistrian University of Athens, 157 80 Athens, Greece.

Congenital myopathies (CMs) constitute a group of heterogenous rare inherited muscle diseases with different incidences. They are traditionally grouped based on characteristic histopathological findings revealed on muscle biopsy. In recent decades, the ever-increasing application of modern genetic technologies has not just improved our understanding of their pathophysiology, but also expanded their phenotypic spectrum and contributed to a more genetically based approach for their classification. Read More

Neuromuscul Disord 2020 May 16;30(5):360-367. Epub 2020 Apr 16.

Department of Pathology, School of Medicine, University of California San Diego, La Jolla, CA 92093-0709, USA. Electronic address:

The collagen VI-related muscular dystrophies in people include a broad spectrum of diseases ranging from the severe Ullrich congenital muscular dystrophy to the mild Bethlem myopathy. Clinical features are attributable to both muscle and connective tissue and include progressive muscle weakness and respiratory failure, hyperlaxity of distal joints, and progressive contracture of large joints. Here we describe two different COL6A3 pathogenic variants in Labrador Retriever dogs that result in autosomal recessive or autosomal dominant congenital myopathies with hyperlaxity of distal joints and joint contracture, similar to the condition in people. Read More

NPJ Regen Med 2020 11;5:10. Epub 2020 May 11.

2Biomedical Research Centre, Department of Medical Genetics, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC Canada.

Skeletal muscle is an ideal target for cell therapy. The use of its potent stem cell population in the form of autologous intramuscular transplantation represents a tantalizing strategy to slow the progression of congenital muscle diseases (such as Duchenne Muscular Dystrophy) or regenerate injured tissue following trauma. The syncytial nature of skeletal muscle uniquely permits the engraftment of stem/progenitor cells to contribute to new myonuclei and restore the expression of genes mutated in myopathies. Read More

Genes (Basel) 2020 05 11;11(5). Epub 2020 May 11.

Genetics Department Hospital de Sant Pau, IIB Sant Pau, 08041 Barcelona, Spain.

The term neuromuscular disorder (NMD) includes many genetic and acquired diseases and differential diagnosis can be challenging. Next-generation sequencing (NGS) is especially useful in this setting given the large number of possible candidate genes, the clinical, pathological, and genetic heterogeneity, the absence of an established genotype-phenotype correlation, and the exceptionally large size of some causative genes such as , and We evaluated the diagnostic value of a custom targeted next-generation sequencing gene panel to study the mutational spectrum of a subset of NMD patients in Spain. In an NMD cohort of 207 patients with congenital myopathies, distal myopathies, congenital and adult-onset muscular dystrophies, and congenital myasthenic syndromes, we detected causative mutations in 102 patients (49. Read More

Ann Neurol 2020 May 13. Epub 2020 May 13.

Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.

Objective: A hitherto undescribed phenotype of early onset muscular dystrophy associated with sensorineural hearing loss and primary ovarian insufficiency was initially identified in 2 siblings and in subsequent patients with a similar constellation of findings. The goal of this study was to understand the genetic and molecular etiology of this condition.

Methods: We applied whole exome sequencing (WES) superimposed on shared haplotype regions to identify the initial biallelic variants in GGPS1 followed by GGPS1 Sanger sequencing or WES in 5 additional families with the same phenotype. Read More

Brain Dev 2020 Aug 7;42(7):539-545. Epub 2020 May 7.

Department of Paediatric Neurology, School of Medicine, Dokuz Eylul University, Izmir, Turkey.

Background: Congenital disorders of glycosylation (CDG) is a heterogeneous group of congenital metabolic diseases with multisystem clinical involvement. ALG3-CDG is a very rare subtype with only 24 cases reported so far.

Case: Here, we report two siblings with dysmorphic features, growth retardation, microcephaly, intractable epilepsy, and hemangioma in the frontal, occipital and lumbosacral regions. Read More

Orphanet J Rare Dis 2020 May 7;15(1):113. Epub 2020 May 7.

National Institute of Nursing Research, National Institutes of Health, Bethesda, MD, 20892, USA.

Background: Pathogenic variations in the gene encoding the skeletal muscle ryanodine receptor (RyR1) are associated with malignant hyperthermia (MH) susceptibility, a life-threatening hypermetabolic condition and RYR1-related myopathies (RYR1-RM), a spectrum of rare neuromuscular disorders. In RYR1-RM, intracellular calcium dysregulation, post-translational modifications, and decreased protein expression lead to a heterogenous clinical presentation including proximal muscle weakness, contractures, scoliosis, respiratory insufficiency, and ophthalmoplegia. Preclinical model systems of RYR1-RM and MH have been developed to better understand underlying pathomechanisms and test potential therapeutics. Read More

Arch Med Sci Atheroscler Dis 2019 2;4:e252-e263. Epub 2019 Dec 2.

Cardiology Department, Onassis Cardiac Surgery Center, Athens, Greece.

Rhabdomyolysis (RM), a fortunately rare disease of the striated muscle cells, is a complication of non-traumatic (congenital (glycogen storage disease, discrete mitochondrial myopathies and various muscular dystrophies) or acquired (alcoholic myopathy, systemic diseases, arterial occlusion, viral illness or bacterial sepsis)) and traumatic conditions. Additionally, RM can occur in some individuals under specific circumstances such as toxic substance use and illicit drug abuse. Lipid-lowering drugs in particular are capable of causing RM. Read More

Neuromuscul Disord 2020 Apr 24;30(4):336-339. Epub 2020 Feb 24.

Department of Neuropediatrics and Muscle Disorders, Faculty of Medicine, Medical Center - University of Freiburg, Freiburg, Germany; Centro Nacional de Análisis Genómico (CNAG-CRG), Center for Genomic Regulation, Barcelona Institute of Science and Technology (BIST), Barcelona, Catalonia, Spain; Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Canada; Department of Medicine, Division of Neurology, The Ottawa Hospital, Ottawa, Canada.

Congenital myasthenic syndromes (CMS) are a group of inherited disorders caused by mutations in genes encoding proteins essential for neuromuscular transmission. CMS is characterized by fatigable muscle weakness with onset at birth or in early childhood; rarely, symptoms may present later. The most frequently involved proteins are choline acetyltransferase, the endplate species of acetylcholinesterase and the acetylcholine receptor subunits. Read More

Mol Genet Genomic Med 2020 Apr 30:e1229. Epub 2020 Apr 30.

Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.

Background: Autosomal recessive or compound heterozygous mutations in KLHL40 cause nemaline myopathy 8, which is one of the most severe forms of nemaline myopathy. The KLHL40 c.1516A>C variant has recently been reported as a founder mutation in southern Chinese. Read More

Sci Rep 2020 Apr 29;10(1):7255. Epub 2020 Apr 29.

Department of Creative IT Engineering, Pohang University of Science and Technology, San 31, Pohang, Gyeongbuk, Republic of Korea.

The incidences of various esophageal diseases (e.g., congenital esophageal stenosis, tracheoesophageal fistula, esophageal atresia, esophageal cancer) are increasing, but esophageal tissue is difficult to be recovered because of its weak regenerative capability. Read More

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2020 May;37(5):497-500

Department of Genetics, Luoyang Maternal and Child Health Care Center, Luoyang, Henan 471000, China.

Objective: To detect pathological variant in a Chinese pedigree affected with congenital contractural arachnodactyly (CCA).

Methods: Next generation sequencing (NGS) was used to scan the whole exome of the proband. Potential variant of the FBN2 gene was also detected in all members of the pedigree and 100 healthy controls by Sanger sequencing. Read More

Pigment Cell Melanoma Res 2020 Apr 23. Epub 2020 Apr 23.

Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain.

Congenital melanocytic nevi (CMN) are cutaneous malformations whose prevalence is inversely correlated with projected adult size. CMN are caused by somatic mutations, but epidemiological studies suggest that germline genetic factors may influence CMN development. In CMN patients from the U. Read More

Int J Prosthodont 2020 May/Jun;33(3):347-353

Microstomia is a clinical condition of reduced mouth opening that can be acquired or congenital in origin. Problems associated with microstomia can be related to function, esthetics, or both. Management of microstomia due to facial burns is complex due to the presence of hypertrophic and contracture scars. Read More

Medicine (Baltimore) 2020 Apr;99(16):e19813

Yinfeng Medical Laboratory, Jinan Shandong.

Rationale: Wiedemann-Steiner syndrome (WDSTS, online mendelian inheritance in man 605130) is a rare autosomal dominant disorder characterized by hypertrichosis cubiti. Here, we report a Chinese boy who do not show the characteristic of hypertrichosis cubiti, and was misdiagnosed as blepharophimosis-ptosis-epicanthus inversus syndrome at first. We found a de novo frameshift mutation (p. Read More

Discoveries (Craiova) 2019 Mar 31;7(1):e90. Epub 2019 Mar 31.

Department of Chemical Engineering and Materials Science, Wayne State University, Detroit, MI, USA.

Skeletal muscle tissue has inherent capacity for regeneration in response to minor injuries. However, in the case of severe trauma, tumor ablations, or in congenital muscle defects, these myopathies can cause irreversible loss of muscle mass and function, a condition referred to as volumetric muscle loss (VML). The natural muscle repair mechanisms are overwhelmed, prompting the search for new muscle regenerative strategies, such as using biomaterials that can provide regenerative signals to either transplanted or host muscle cells. Read More

Ann Clin Transl Neurol 2020 May 19;7(5):846-854. Epub 2020 Apr 19.

Laboratoire de Génétique Moléculaire, CHU de Montpellier, Montpellier, France.

Congenital titinopathies are myopathies with variable phenotypes and inheritance modes. Here, we fully characterized, using an integrated approach (deep phenotyping, muscle morphology, mRNA and protein evaluation in muscle biopsies), two siblings with congenital multicore myopathy harboring three TTN variants predicted to affect titin stability and titin-myosin interactions. Muscle biopsies showed multicores, type 1 fiber uniformity and sarcomeric structure disruption with some thick filament loss. Read More

Pediatr Pulmonol 2020 Jun 16;55(6):1490-1494. Epub 2020 Apr 16.

Pediatric Pulmonology and Respiratory Intermediate Care Unit, Sleep and Long-Term Ventilation Unit, Department of Pediatrics, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

Introduction And Objectives: Patients with neuromuscular disease (NMD) are often exposed to ionizing radiations which could be reduced if a noninvasive and reliable diagnostic method is identified. The major aim of this study was to compare the use of chest X-ray (CXR) with lung ultrasound (LUS) in pediatric patients with NMD, to identify pulmonary atelectasis (PA).

Materials And Methods: A prospective study was conducted on children affected by NMD. Read More

Semin Neurol 2020 Jun 15;40(3):335-341. Epub 2020 Apr 15.

Department of Neurology, University of California San Francisco, San Francisco, California.

In the past decade, the number of genes linked to neuromuscular diseases of childhood has expanded dramatically, and this genetic information is forming the basis for gene-specific and even mutation-specific therapies. At the forefront of these advances are the two recently approved treatments for spinal muscular atrophy: one, an antisense oligonucleotide that modifies splicing of the SMN2 gene, and, the other, a gene therapy vector that delivers the gene to motor neurons, both of which are allowing patients to acquire developmental milestones previously unseen in this fatal disease. This review highlights these advances and emerging targeted therapies for Duchenne muscular dystrophy and centronuclear myopathy, while also covering enzyme replacement therapy and small molecule-based targeted therapies for conditions such as Pompe's disease and congenital myasthenic syndromes. Read More

BMC Musculoskelet Disord 2020 Apr 13;21(1):235. Epub 2020 Apr 13.

Institute of Health and Society, University of Oslo, P.O. Box 1089, N-0318, Oslo, Blindern, Norway.

Background: Physical activity is associated with positive health effects, but individuals with neuromuscular disease (NMD) may experience constraints being physically active. There is a gap in the literature on the activity level of people with NMDs, and therefore we did a study to determine the physical activity level in people with Limb-Girdle muscular dystrophy (LGMD) and Charcot-Marie-Tooth disease (CMT).

Methods: This study used a cross-sectional design to obtain self-reported physical activity and sitting time among individuals with LGMD and CMT who were recruited from the Norwegian registry for hereditary and congenital neuromuscular diseases. Read More

Int J Mol Sci 2020 Apr 8;21(7). Epub 2020 Apr 8.

Department of Clinical and Experimental Cardiology, Heart Center, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.

Patients with very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) can present with life-threatening cardiac arrhythmias. The pathophysiological mechanism is unknown. We reprogrammed fibroblasts from one mildly and one severely affected VLCADD patient, into human induced pluripotent stem cells (hiPSCs) and differentiated these into cardiomyocytes (VLCADD-CMs). Read More

Regen Eng Transl Med 2020 Mar 16;6(1):62-68. Epub 2019 Jul 16.

Department of Molecular & Integrative Physiology, 2025 BSRB 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200.

Volumetric muscle loss (VML) is defined as the loss of skeletal muscle tissue which exceeds the body's repair capabilities leading to sustained functional deficits over time. Some etiologies leading to VML include traumatic injuries, congenital diseases, and degenerative myopathies. Currently, the lack of standardized animal models prevents an appropriate estimation of the severity of injury capable of exceeding self-regeneration. Read More

Turk J Pediatr 2020 ;62(1):130-135

Division of Child Neurology, Department of Pediatrics, Ege University Faculty of Medicine, İzmir, Turkey.

Dropped head syndrome can be seen in many neuromuscular diseases. However, there are very few diseases in which neck extensors are weak among neuromuscular diseases. A 7 years old boy who had weakness of the neck extensor muscles, creatinine kinase elevation and dystrophy findings in biopsy followed up with the preliminary diagnosis of muscular dystrophy is presented. Read More

Cells 2020 Mar 31;9(4). Epub 2020 Mar 31.

Institut de Myologie, Centre de Recherche en Myologie, Sorbonne Université, INSERM UMRS974, F-75651 Paris CEDEX 13, France.

encodes for Lamin A/C, type V intermediate filaments that polymerize under the inner nuclear membrane to form the nuclear lamina. A small fraction of Lamin A/C, less polymerized, is also found in the nucleoplasm. Lamin A/C functions include roles in nuclear resistance to mechanical stress and gene regulation. Read More

Hum Mol Genet 2020 May;29(8):1330-1339

Departments of Biomedicine, Basel University Hospital, 4031 Basel, Switzerland.

Mutations in the RYR1 gene are the most common cause of human congenital myopathies, and patients with recessive mutations are severely affected and often display ptosis and/or ophthalmoplegia. In order to gain insight into the mechanism leading to extraocular muscle (EOM) involvement, we investigated the biochemical, structural and physiological properties of eye muscles from mouse models we created knocked-in for Ryr1 mutations. Ex vivo force production in EOMs from compound heterozygous RyR1p. Read More

Clin Genet 2020 Jun 6;97(6):878-889. Epub 2020 Apr 6.

Department of Neurology, Peking University First Hospital, Beijing, China.

Hereditary nemaline myopathy (NM) is one of the most common congenital myopathies with the histopathological findings of nemaline bodies. We used targeted next-generation sequencing to identify causative mutations in 48 NM patients with confirmed myopathological diagnosis, analyze the mutational spectrum and phenotypic features. Furthermore, reverse transcription polymerase chain reaction (RT-PCR) was used to confirm the pathogenic effect of one nebulin (NEB) splicing variant. Read More

J Appl Genet 2020 May 18;61(2):179-186. Epub 2020 Mar 18.

Department of Genetics and Animal Breeding, Poznan University of Life Sciences, Poznan, Poland.

Rapid progress in knowledge of the organization of the dog genome has facilitated the identification of the mutations responsible for numerous monogenic diseases, which usually present a breed-specific distribution. The majority of these diseases have clinical and molecular counterparts in humans. The affected dogs have thus become valuable models for preclinical studies of gene therapy for problems such as eye diseases, immunodeficiency, lysosomal storage diseases, hemophilia, and muscular dystrophy. Read More

Hum Mol Genet 2020 May;29(7):1192-1204

Department of Human Genetics, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.

Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause of end-stage kidney disease in children. While the genetic aberrations underlying CAKUT pathogenesis are increasingly being elucidated, their consequences on a cellular and molecular level commonly remain unclear. Recently, we reported rare heterozygous deleterious LIFR variants in 3. Read More

Front Pediatr 2020 27;8:72. Epub 2020 Feb 27.

Department of Paediatrics, Medical School, Comenius University and National Institute of Children's Diseases, Bratislava, Slovakia.

Myhre syndrome is a rare condition caused by a mutation in the gene, which leads to a defective TGF-β/BMP signaling, resulting in the proliferation of abnormal fibrous tissues. Clinically, patients with Myhre syndrome manifest with defects of connective tissue (skin, muscles, joints), and cardiovascular and neurological impairment. In our report, we present a case of a 16-year-old female with skeletal abnormalities, reduced articular mobility, skin, and muscular hypertrophy and cardiovascular defects characteristic of Myhre syndrome. Read More

Hum Mol Genet 2020 Mar 11. Epub 2020 Mar 11.

Division of Newborn Medicine.

Cofilin-2 is an actin-binding protein that is predominantly expressed in skeletal and cardiac muscles and belongs to the AC group of proteins which includes cofilin-1 and destrin. In humans, cofilin-2 (CFL2) mutations have been associated with congenital myopathies that include nemaline and myofibrillar myopathy. To understand the pathogenicity of the human CFL2 mutation, p. Read More

J Foot Ankle Res 2020 Mar 2;13(1):10. Epub 2020 Mar 2.

Department of Physiotherapy, The University of Melbourne, Parkville, Vic, Australia.

Background: Weakness is the primary impairment in paediatric neuromuscular diseases, impacting gait and gait-related functional activities in ambulant children affected by these rare and often degenerative diseases. Gait speed is an indicator of health and disability, yet gait is a complex, multi-faceted activity. Using the International Classification of Function, Health and Disability (ICF) model, assessment of gait and functional ambulation should consider the impairments, activity limitations and participation restrictions due to disease, and factors related to the environment and the individual person. Read More

J Med Case Rep 2020 Feb 21;14(1):34. Epub 2020 Feb 21.

Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitário de São João EPE, Alameda Professor Hernâni Monteiro, 4202-451, Porto, Portugal.

Background: Lipodystrophies are a group of diseases which are characterized by abnormal adipose tissue deposition and are frequently associated with metabolic changes. Congenital generalized lipodystrophy is an autosomal recessive syndrome, with a prevalence < 1:10 million. Acromegaly is a rare disease, secondary to the chronic hypersecretion of growth hormone and insulin-like growth factor-1, with characteristic metabolic and somatic effects. Read More

Digit J Ophthalmol 2019 Apr 17;25(4):59-64. Epub 2019 Nov 17.

Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis.

A 4-year-old girl with a history of Pearson marrow-pancreas syndrome presenting with severe, progressive photophobia was found to have bilateral, diffuse corneal thickening and peripheral pigmentary retinopathy. She underwent Descemet stripping automated endothelial keratoplasty (DSAEK) surgery in both eyes using a modified suture pull-through technique. Postoperatively there was no evidence of cataract formation or graft detachment; her corneas thinned, and her photophobia improved dramatically. Read More

Acta Neuropathol Commun 2020 02 17;8(1):18. Epub 2020 Feb 17.

Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, Western Australia, Australia.

Nemaline myopathy (NM) caused by mutations in the gene encoding nebulin (NEB) accounts for at least 50% of all NM cases worldwide, representing a significant disease burden. Most NEB-NM patients have autosomal recessive disease due to a compound heterozygous genotype. Of the few murine models developed for NEB-NM, most are Neb knockout models rather than harbouring Neb mutations. Read More

Hum Genet 2020 Apr 13;139(4):483-498. Epub 2020 Feb 13.

Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.

Biallelic variants in TOR1AIP1, encoding the integral nuclear membrane protein LAP1 (lamina-associated polypeptide 1) with two functional isoforms LAP1B and LAP1C, have initially been linked to muscular dystrophies with variable cardiac and neurological impairment. Furthermore, a recurrent homozygous nonsense alteration, resulting in loss of both LAP1 isoforms, was identified in seven likely related individuals affected by multisystem anomalies with progeroid-like appearance and lethality within the 1st decade of life. Here, we have identified compound heterozygosity in TOR1AIP1 affecting both LAP1 isoforms in two unrelated individuals affected by congenital bilateral hearing loss, ventricular septal defect, bilateral cataracts, mild to moderate developmental delay, microcephaly, mandibular hypoplasia, short stature, progressive muscular atrophy, joint contractures and severe chronic heart failure, with much longer survival. Read More

Cells 2020 Feb 11;9(2). Epub 2020 Feb 11.

CNR-Institute of Molecular Genetics "Luigi Luca Cavalli-Sforza"-Unit of Bologna, 40136 Bologna, Italy.

Mutations in collagen VI genes cause two major clinical myopathies, Bethlem myopathy (BM) and Ullrich congenital muscular dystrophy (UCMD), and the rarer myosclerosis myopathy. In addition to congenital muscle weakness, patients affected by collagen VI-related myopathies show axial and proximal joint contractures, and distal joint hypermobility, which suggest the involvement of tendon function. To gain further insight into the role of collagen VI in human tendon structure and function, we performed ultrastructural, biochemical, and RT-PCR analysis on tendon biopsies and on cell cultures derived from two patients affected with BM and UCMD. Read More

BMC Pediatr 2020 Feb 6;20(1):57. Epub 2020 Feb 6.

Neuromuscular and Neurogenetic Disorders of Childhood Section, Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 10, Room 2B 39, MSC 1477, 10 Center Drive, Bethesda, MD, 20892, USA.

Background: Only a few small studies have previously reported episodes of hypoglycemia in children with neuromuscular diseases; however, there has been no broader investigation into the occurrence of hypoglycemia in children with congenital muscle disease (CMD).

Methods: Pediatric patients enrolled in the CMD International Registry (CMDIR) with a history of hypoglycemia were included in this retrospective review. Hypoglycemic episodes and associated clinical and biochemical characteristics were characterized. Read More

Am J Physiol Cell Physiol 2020 Apr 5;318(4):C709-C718. Epub 2020 Feb 5.

Sorbonne Université, Institut de Biologie Paris-Seine, CNRS UMR 8256, INSERM ERL U1164, Biological Adaptation and Ageing, Paris, France.

This review analyzes data concerning patients with cardiomyopathies or skeletal myopathies associated with a variation in the intermediate filament (IF) synemin gene (), also referred to as desmuslin (). Molecular studies demonstrate that synemin copolymerizes with desmin and vimentin IF and interacts with vinculin, α-actinin, α-dystrobrevin, dystrophin, talin, and zyxin. It has been found that synemin is an A-kinase-anchoring protein (AKAP) that anchors protein kinase A (PKA) and modulates the PKA-dependent phosphorylation of several cytoskeletal substrates such as desmin. Read More

Int J Appl Basic Med Res 2020 Jan-Mar;10(1):3-7. Epub 2020 Jan 3.

Department of Cardiology, U.N. Mehta Institute of Cardiology and Research Center, Civil Hospital Campus, Ahmedabad, Gujarat, India.

Aims: Patent ductus arteriosus (PDA) is one of the most commonly seen congenital heart diseases prevalent today. The aim of this study is to evaluate the safety and efficacy of transcatheter closure of hypertensive ductus at long-term follow-up.

Materials And Methods: Transcatheter closure was attempted in 52 patients with hypertensive ductus arteriosus. Read More