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Case Rep Ophthalmol 2021 Jan-Apr;12(1):174-181. Epub 2021 Apr 12.

Division of Neurology, Department of Medicine, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.

Mitochondrial neurogastrointestinal encephalopathy disease (MNGIE) is a rare autosomal recessive condition characterized by gastrointestinal dysmotility, external ophthalmoplegia, leukoencephalopathy, and sensorimotor neuropathy. A 31-year-old man was referred for a 1-year history of horizontal diplopia related to a large exotropia from chronic progressive external ophthalmoplegia. MRI revealed a diffuse leukoencephalopathy and his 3-year history of chronic intermittent diarrhea, cachexia, and diffuse sensory more than motor peripheral neuropathy led to a unifying clinical diagnosis of MNGIE. Read More

Klin Monbl Augenheilkd 2021 Apr 30;238(4):414-417. Epub 2021 Apr 30.

Ophthalmology, Jules Gonin Eye Hospital, Lausanne, Switzerland.

Background: The mitochondrial DNA (mtDNA) A3243G point mutation encompasses a heterogenous group of disorders including mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), maternally inherited diabetes and deafness (MIDD), and, rarely, chronic progressive external ophthalmoplegia (CPEO). Regardless of the clinical phenotype, a specific retinopathy has been associated with the presence of this mitochondrial DNA mutation. We present six female patients exhibiting retinopathy of the A3243G point mutation at various stages. Read More

Am J Ophthalmol Case Rep 2021 Jun 17;22:101073. Epub 2021 Mar 17.

Department of Orbit, Plastic and Lacrimal Surgery, Royal Victorian Eye and Ear Hospital, 32 Gisborne Street, East Melbourne, Victoria, Australia.

Purpose: To describe two patients with bilateral ptosis, ophthalmoplegia, cataracts and corneal endothelial disease requiring corneal transplantation.

Observations: Histopathological analysis of muscle biopsy samples from both patients identified features consistent with a mitochondrial cytopathy. A single multigenic mitochondrial deoxyribonucleic acid (DNA) deletion was detected in the first patient. Read More

Invest Ophthalmol Vis Sci 2021 Mar;62(3):22

Department of Ophthalmology and Visual Sciences, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States.

Mitochondrial function is essential for the viability of aerobic eukaryotic cells, as mitochondria provide energy through the generation of adenosine triphosphate (ATP), regulate cellular metabolism, provide redox balancing, participate in immune signaling, and can initiate apoptosis. Mitochondria are dynamic organelles that participate in a cyclical and ongoing process of regeneration and autophagy (clearance), termed mitophagy specifically for mitochondrial (macro)autophagy. An imbalance in mitochondrial function toward mitochondrial dysfunction can be catastrophic for cells and has been characterized in several common ophthalmic diseases. Read More

Mol Genet Metab Rep 2021 Jun 25;27:100733. Epub 2021 Feb 25.

Department of Medical Genetics, Hospital de Pediatría "Juan P. Garrahan", Combate de los Pozos 1881, Buenos Aires 1245, Argentina.

Objective: To describe the clinical and molecular features of a group of Argentinian pediatric patients with mitochondrial DNA (mtDNA) disorders, and to evaluate the results of the implementation of a classical approach for the molecular diagnosis of mitochondrial diseases.

Methods: Clinical data from 27 patients with confirmed mtDNA pathogenic variants were obtained from a database of 89 patients with suspected mitochondrial disease, registered from 2014 to 2020. Clinical data, biochemical analysis, neuroimaging findings, muscle biopsy and molecular studies were analyzed. Read More

Mitochondrion 2021 03 21;57:205-212. Epub 2021 Jan 21.

Research Centre for Medical Genetics, Russia.

Currently, pathogenic variants in more than 25 nuclear genes, involved in mtDNA maintenance, are associated with human disorders. mtDNA maintenance disorders manifest with a wide range of phenotypes, from severe infantile-onset forms of myocerebrohepatopathy to late-onset forms of myopathies, chronic progressive external ophthalmoplegia, and parkinsonism. This study represents the results of molecular genetic analysis and phenotypes of 102 probands with mtDNA maintenance disorders. Read More

J Mol Neurosci 2021 Jan 19. Epub 2021 Jan 19.

Department of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.

Polymerase γ catalytic subunit (POLG), a nuclear gene, encodes the enzyme responsible for mitochondrial DNA (mtDNA) replication. POLG mutations are a major cause of inherited mitochondrial diseases. They present with varied phenotypes, age of onset, and severity. Read More

Genes (Basel) 2020 Dec 31;12(1). Epub 2020 Dec 31.

Department of Neurology, Medical University of Warsaw, Banacha 1a, 02-097 Warsaw, Poland.

Mitochondrial encephalomyopathies comprise a group of heterogeneous disorders resulting from impaired oxidative phosphorylation (OxPhos). Among a variety of symptoms progressive external ophthalmoplegia (PEO) seems to be the most common. The aim of this study is to present clinical and genetic characteristics of Polish patients with PEO. Read More

JAMA Ophthalmol 2021 02;139(2):234-235

Department of Ophthalmology and Visual Sciences, Montefiore Medical Center, Bronx, New York.

Ophthalmic Genet 2021 02 24;42(1):100. Epub 2020 Nov 24.

Ophthalmic Genetics & Visual Function Branch, National Eye Institute, National Institutes of Health , Bethesda, Maryland, USA.

Acta Ophthalmol 2021 Mar 15;99(2):e274-e280. Epub 2020 Nov 15.

Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.

Purpose: To elucidate the patterns of strabismus and ophthalmoplegia associated with chronic progressive external ophthalmoplegia (CPEO) confirmed by mitochondrial DNA (mtDNA) deletions in Asians.

Methods: A total of 10 patients confirmed to have mtDNA deletion associated with CPEO were included. Long-range PCR encompassing the entire mtDNA was carried out. Read More

Neuroradiology 2021 01 3;63(1):9-10. Epub 2020 Nov 3.

Neuroradiology Unit, Imaging Department, Bambino Gesù Children's Hospital, Piazza Sant'Onofrio 4, 00165, Rome, Italy.

Front Genet 2020 2;11:547638. Epub 2020 Oct 2.

Copenhagen Neuromuscular Center, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

It is generally accepted that patients with chronic progressive ophthalmoplegia caused by single large-scale deletion (SLD) of mitochondrial DNA (mtDNA) only harbor mutation in skeletal and eye muscles. The aim of this study was to investigate the presence and the level of heteroplasmy of mtDNA deletions in mitotic tissues of patients displaying mtDNA deletion of mitotic tissues in patients with SLDs and pure muscle phenotype. MtDNA mutation load was studied in three mitotic (urine epithelial cells, buccal mucosa, and blood) and one postmitotic (skeletal muscle) tissues in 17 patients with SLDs of mtDNA and pure muscle involvement. Read More

Gene 2021 Feb 27;769:145237. Epub 2020 Oct 27.

Korean Genomics Center (KOGIC), UNIST, Republic of Korea; Department of Biomedical Engineering, School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan, Republic of Korea.

Egyptians are at a crossroad between Africa and Eurasia, providing useful genomic resources for analyzing both genetic and environmental factors for future personalized medicine. Two personal Egyptian whole genomes have been published previously by us and here nine female whole genome sequences with clinical information have been added to expand the genomic resource of Egyptian personal genomes. Here we report the analysis of whole genomes of nine Egyptian females from different regions using Illumina short-read sequencers. Read More

Neuromuscul Disord 2020 11 14;30(11):897-903. Epub 2020 Oct 14.

Department of Neurology, Faculdade de Medicina da Universidade de São Paulo (FMUSP), Av. Dr. Enéas Carvalho Aguiar 255, 05403-900 São Paulo SP, Brazil. Electronic address:

This study was designed to analyze the sensitivity, specificity, and accuracy of jitter parameters combined with repetitive nerve stimulation (RNS) in congenital myasthenic syndrome (CMS), chronic progressive external ophthalmoplegia (CPEO), and congenital myopathies (CM). Jitter was obtained with a concentric needle electrode during voluntary activation of the Orbicularis Oculi muscle in CMS (n = 21), CPEO (n = 20), and CM (n = 18) patients and in controls (n = 14). RNS (3 Hz) was performed in six different muscles for all patients (Abductor Digiti Minimi, Tibialis Anterior, upper Trapezius, Deltoideus, Orbicularis Oculi, and Nasalis). Read More

Hum Mutat 2020 11;41(11):2014-2015

Division of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy.

Hum Mutat 2020 11;41(11):2012-2013

Messerli Institute, Klinikum Landstrasse, Vienna, Austria.

Invest Ophthalmol Vis Sci 2020 10;61(12):14

Center for Physiology and Pathophysiology, Institute of Vegetative Physiology, University of Köln, Köln, Germany.

Purpose: The purpose of this study was to gain insights on the pathogenesis of chronic progressive external ophthalmoplegia, thus we investigated the vulnerability of five extra ocular muscles (EOMs) fiber types to pathogenic mitochondrial DNA deletions in a mouse model expressing a mutated mitochondrial helicase TWINKLE.

Methods: Consecutive pairs of EOM sections were analyzed by cytochrome C oxidase (COX)/succinate dehydrogenase (SDH) assay and fiber type specific immunohistochemistry (type I, IIA, IIB, embryonic, and EOM-specific staining).

Results: The mean average of COX deficient fibers (COX-) in the recti muscles of mutant mice was 1. Read More

Invest Ophthalmol Vis Sci 2020 10;61(12):12

Jonas Children's Vision Care, Department of Ophthalmology, Columbia University Irving Medical Center, New York, New York, United States.

Purpose: The purpose of this paper was to discuss manifestations of primary mitochondrial dysfunctions and whether the retinal pigment epithelium or the photoreceptors are preferentially affected.

Methods: A retrospective analysis was performed of patients with clinically and laboratory confirmed diagnoses of maternally inherited diabetes and deafness (MIDD) or Kearns-Sayre syndrome (KSS). Patients underwent full ophthalmic examination, full-field electroretinogram, and multimodal imaging studies, including short-wavelength autofluorescence, spectral domain-optical coherence tomography, and color fundus photography. Read More

Mol Genet Genomic Med 2020 11 8;8(11):e1509. Epub 2020 Oct 8.

Genetics, Department of Medicine, Genetics and Molecular Medicine Research Group, Universidad del Norte, Barranquilla, Colombia.

Background: Kearns-Sayre Syndrome (KSS) and Pearson Marrow-Pancreas Syndrome (PMPS) are among the classic phenotypes caused by mitochondrial DNA (mtDNA) deletions. KSS is a rare mitochondrial disease defined by a classic triad of progressive external ophthalmoplegia, atypical pigmentary retinopathy, and onset before 20 years. PMPS presents in the first year of life with bone marrow failure and exocrine pancreatic dysfunction, and can evolve into KSS later in life. Read More

Neuroradiology 2021 01 7;63(1):7-8. Epub 2020 Oct 7.

Department of Cardiothoracic Science, Hospital S. Maria della Misericordia, Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italy.

Front Neurol 2020 8;11:1000. Epub 2020 Sep 8.

Neurology Department, Children's Hospital of Fudan University, Shanghai, China.

Mitochondrial myopathy in children has notable clinical and genetic heterogeneity, but detailed data is lacking. In this study, we retrospectively reviewed the clinical presentation, laboratory investigation, genetic and histopathological characteristics, and follow-ups of 21 pediatric mitochondrial myopathy cases from China. Twenty-four patients suspected with mitochondrial myopathy were enrolled initially and 21 were genetically identified. Read More

DNA Cell Biol 2020 10 28;39(10):1908-1911. Epub 2020 Sep 28.

ENT Institute and Otolaryngology Department of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China.

Ophthalmic Genet 2021 02 25;42(1):99. Epub 2020 Sep 25.

Klinik Landstrasse, Messerli Institute , Vienna, Austria.

DNA Cell Biol 2020 10 1;39(10):1907-1908. Epub 2020 Sep 1.

Krankenanstalt Rudolfstiftung, Messerli Institute, Vienna, Austria.

Acta Neurol Scand 2021 Jan 19;143(1):103-108. Epub 2020 Sep 19.

Department of Laboratory Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Objectives: To describe two patients with progressive external ophthalmoplegia (PEO) and mitochondrial myopathy associated with mutations in mitochondrial DNA, encoding the tRNA gene (MT-TN), which have not previously been published with clinical descriptions.

Materials & Methods: Two unrelated patients with PEO were clinically examined. Muscle biopsy was performed and investigated by exome sequencing, enzyme histochemistry, and immunohistochemistry. Read More

J Neuroophthalmol 2021 03;41(1):136-137

Krankenanstalt Rudolfstiftung, Messerli Institute, Vienna, Austria.

J Neuroophthalmol 2021 03;41(1):137-138

Department of Ophthalmology, Columbia University Irving Medical Center, New York, New York.

Neurol India 2020 Jul-Aug;68(4):760-768

Department of Neurology, Zanjan University of Medical Sciences, Vali-e-Asr Hospital, Zanjan, Iran.

Progressive external ophthalmoplegia (PEO) is a slowly progressive myopathy characterized by extraocular muscles involvement, leading to frozen eyes without diplopia. The pattern of inheritance may be mitochondrial, autosomal dominant or, rarely, autosomal recessive. Sporadic forms were also reported. Read More

Eur J Ophthalmol 2020 Aug 27:1120672120952344. Epub 2020 Aug 27.

Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Purpose: To determine possible complications and efficacy of ptosis surgery in a series of chronic progressive external ophthalmoplegia (CPEO) patients with healthy tear film.

Method: It is a prospective interventional study on 24 eyes from 12 patients with the diagnosis of CPEO and ptosis. Pre-operatively, tear breakup test (TBUT) and Schirmer test were performed to assess lacrimal function unit. Read More