Mitochondrial Disorder: Kearns-Sayre Syndrome

Tsang, Stephen H.; Aycinena, Alicia R. P.; Sharma, Tarun

doi:10.1007/978-3-319-95046-4_30

Cited by 34 publications

(26 citation statements)

References 1 publication

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“…Retinal degeneration can be accompanied by vascular attenuation, which becomes more noticeable with disease progression and increasing patient age . Pigmentary changes can be seen in CPEO, specifically in Kearns‐Sayre syndrome . However, these changes can also be detected among patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke‐like episodes, maternally inherited diabetes and deafness, mitochondrial neurogastrointestinal encephalomyopathy, OPA1 mutations, maternally inherited Leigh syndrome, and neuropathy, ataxia, and retinitis pigmentosa .…”

Section: Discussionmentioning

confidence: 99%

SSBP1 mutations in dominant optic atrophy with variable retinal degeneration

Jurkutė

Leu

Pogoda

et al. 2019

Annals of Neurology

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Objective: Autosomal dominant optic atrophy (ADOA) starts in early childhood with loss of visual acuity and color vision deficits. OPA1 mutations are responsible for the majority of cases, but in a portion of patients with a clinical diagnosis of ADOA, the cause remains unknown. This study aimed to identify novel ADOA-associated genes and explore their causality. Methods: Linkage analysis and sequencing were performed in multigeneration families and unrelated patients to identify disease-causing variants. Functional consequences were investigated in silico and confirmed experimentally using the zebrafish model. Results: We defined a new ADOA locus on 7q33-q35 and identified 3 different missense variants in SSBP1 (NM_001256510.1; c.113G>A [p.(Arg38Gln)], c.320G>A [p.(Arg107Gln)] and c.422G>A [p.(Ser141Asn)]) in affected individuals from 2 families and 2 singletons with ADOA and variable retinal degeneration. The mutated arginine residues are part of a basic patch that is essential for single-strand DNA binding. The loss of a positive charge at these positions is very likely to lower the affinity of SSBP1 for single-strand DNA. Antisense-mediated knockdown of endogenous ssbp1 messenger RNA (mRNA) in zebrafish resulted in compromised differentiation of retinal ganglion cells. A similar effect was View this article online at wileyonlinelibrary.com.Additional supporting information can be found in the online version of this article.

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Section: Discussionmentioning

confidence: 99%

SSBP1 mutations in dominant optic atrophy with variable retinal degeneration

Jurkutė

Leu

Pogoda

et al. 2019

Annals of Neurology

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“…Several mitochondrial diseases have ophthalmic manifestations, including Kearns-Sayre syndrome (KSS); myoclonic epilepsy with ragged red fibers (MERRF); mitochondrial encephalopathy lactic acidosis stroke (MELAS); neuropathy, ataxia, and retinitis pigmentosa (NARP); LHON; CPEO; and autosomal dominant optic atrophy (DOA). [159][160][161] Many of these diseases have phenotypes related to myopathy due to the high energy demand of sarcomeres, 162,163 and ocular phenotypes can be the first observed in mitochondrial diseases. 164 Mitochondrial diseases give great insight into the effects of altered mitophagy on disease pathology because the mechanism is the result of specific gene mutations.…”

Section: Ocular Phenotypes Of Systemic Mitochondrial Disease Related mentioning

confidence: 99%

Mitophagy: An Emerging Target in Ocular Pathology

Skeie

Nishimura

Wang

et al. 2021

Invest. Ophthalmol. Vis. Sci.

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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. In this article, we review mitochondrial homeostasis in detail, focusing on the balance of mitochondrial dynamics including the processes of fission and fusion, and provide a description of the mechanisms involved in mitophagy. Furthermore, this article reviews investigations of ocular diseases with impaired mitophagy, including Fuchs endothelial corneal dystrophy, primary open-angle glaucoma, diabetic retinopathy, and age-related macular degeneration, as well as several primary mitochondrial diseases with ocular phenotypes that display impaired mitophagy, including mitochondrial encephalopathy lactic acidosis stroke, Leber hereditary optic neuropathy, and chronic progressive external ophthalmoplegia. The results of various studies using cell culture, animal, and human tissue models are presented and reflect a growing awareness of mitophagy impairment as an important feature of ophthalmic disease pathology. As this review indicates, it is imperative that mitophagy be investigated as a targetable mechanism in developing therapies for ocular diseases characterized by oxidative stress and mitochondrial dysfunction.

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“…70, 75-79, Kearns-Sayre syndrome typically includes chronic progressive external ophthalmoplegia, ptosis, and pigmentary retinopathy in individuals less than 20 years of age. 80 Pearson syndrome occurs in infancy, and characteristically includes sideroblastic anemia and exocrine pancreatic dysfunction. 81 Hypomagnesaemia has been described in different mitochondrial syndromes, for instance in patients with Kearns-Sayre syndrome.…”

Section: Tubular Defectsmentioning

confidence: 99%

Mitochondrial Disease and the Kidney With a Special Focus on CoQ10 Deficiency

Schijvens

Kar

Bootsma-Robroeks

et al. 2020

Kidney International Reports

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Mitochondrial Disorder: Kearns-Sayre Syndrome

Cited by 34 publications

References 1 publication

SSBP1 mutations in dominant optic atrophy with variable retinal degeneration

SSBP1 mutations in dominant optic atrophy with variable retinal degeneration

Mitophagy: An Emerging Target in Ocular Pathology

Mitochondrial Disease and the Kidney With a Special Focus on CoQ10 Deficiency

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