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Query: UMLS:C0029089 (ophthalmoplegia)
 3,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report an application of multiprimed polymerase chain reaction (PCR) which allows a rapid, nonradioactive detection of deletions in mitochondrial DNA using EDTA-blood and muscle samples. The use of two primer sets consisting of three forward and five reverse primers, respectively, allows a competitive PCR resulting in significant amplification products only in the presence of deletion-harbouring DNA species. Under the conditions described, deletions causing Kearns-Sayre syndrome (KSS) and progressive external ophthalmoplegia (PEO) have been successfully detected. The location of the primers on mitochondrial DNA used in this study should allow identification and localization of most of the large-scale deletions (i.e. more than 1 kb) of mitochondrial DNA reported so far.
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PMID:Deletion screening of mitochondrial DNA via multiprimer DNA amplification. 802 7

We studied muscle biopsies of 5 patients with Kearns-Sayre syndrome and 3 patients with chronic progressive external ophthalmoplegia all with the common deletion. Steady state levels of normal and deleted mitochondrial DNA (mtDNA) measured in each patient by quantitative PCR were correlated with histochemical and biochemical features. We found that (1) normal mtDNA levels were higher in many patients than in controls; (2) as levels of deleted mtDNA increased, so did levels of normal mtDNA; (3) cytochrome c oxidase (COX) activity and the percentage of COX negative fibers were both related to the levels of deleted mtDNA; and (4) as percentage of ragged red fibers increased, so did levels of total, deleted and normal mtDNA. The quantity of deleted mtDNA plays a key role in determining the severity of COX deficiency, which is responsible for the overaccumulation of mitochondria in muscle.
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PMID:Chronic progressive external ophthalmoplegia: a correlative study of quantitative molecular data and histochemical and biochemical profile. 806 7

We reviewed the ophthalmological and genetic aspects of mitochondrial diseases, a group of multisystem disorders that involve the function and morphology of mitochondria and affect multiple organs including skeletal muscle, central nervous system, heart, and ear. Disease-specific deletion or point mutation of mitochondrial DNA (mtDNA) has been clarified in many clinical entities of the group, and we confirmed that the ocular manifestations, including chronic progressive external ophthalmoplegia, blepharoptosis, retinochoroidal degeneration and optic nerve atrophy, develop in association with either deletion or point mutation of mtDNA. Together with a review of the literature, we describe a case of myoclonic epilepsy and ragged-red fibers with mutation at mtDNA 8344 and insidious bilateral optic atrophy. We also describe cases of myotonic dystrophy which had an abnormal expansion of CTG repeat of chromosome 19 protein kinase gene and showed retinochoroidal degeneration and mitochondrial morphological changes.
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PMID:[Ocular manifestations in mitochondrial DNA abnormalities]. 810 43

We have investigated a 15 year old girl with progressive external ophthalmoplegia, including bilateral ptosis and retinal rod and cone cell dysfunction with atypical retinal pigmentation, complicated by cerebellar ataxia, partial cardiac conduction block, and diabetes mellitus. In infancy she had a severe crisis of bone marrow depression, and as a child she suffered from hypersensitivity to light, increasing fatigue, and vertigo, signs that were initially though to be psychosomatic. Histological examination showed mitochondrial myopathy, and subsequent mitochondrial DNA (mtDNA) analysis showed a deletion of approximately 5500 base pairs in 35 to 40% of her muscle mtDNA. We therefore conclude that this patient has developed the Kearns-Sayre syndrome after a Pearson syndrome-like crisis in her first year of life.
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PMID:Juvenile Kearns-Sayre syndrome initially misdiagnosed as a psychosomatic disorder. 815 37

A 38-yr-old man with external ophthalmoplegia, cardiac conduction abnormalities, hearing loss, and ragged-red fibres in skeletal muscle biopsy, developed severe signs of cardiac failure within a few months. Echocardiography and angiography demonstrated a dilated cardiomyopathy. Ubiquinone 140 mg day-1 did not stop the worsening of the cardiac status and cardiac transplantation was performed. Molecular analysis showed a heteroplasmic 4.5 kb mitochondrial DNA deletion in endomyocardial tissue. Eighteen months later, cardiac evolution is good and neurological status is stable.
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PMID:Cardiac transplantation in an incomplete Kearns-Sayre syndrome with mitochondrial DNA deletion. 818 12

This article describes a 37-year-old woman with progressive external ophthalmoplegia, peripheral neuropathy, and chronic intractable diarrhea. Laboratory studies disclosed lactic acidosis, ragged red fibers lacking cytochrome c oxidase, high-normal muscular mitochondrial enzymes, demyelinating neuropathy, leukoencephalopathy and multiple mitochondrial DNA deletions. This is the fourth patient described with this clinical syndrome, which represents a separate entity among multisystemic mitochondrial disorders. The patient described here is the first with this syndrome to have multiple mitochondrial DNA deletions.
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PMID:Ophthalmoplegia, demyelinating neuropathy, leukoencephalopathy, myopathy, and gastrointestinal dysfunction with multiple deletions of mitochondrial DNA: a mitochondrial multisystem disorder in search of a name. 819 10

Mitochondrial diseases are uniquely interesting from a genetic point of view because mitochondria contain their own DNA (mtDNA) and are capable of synthesizing a small but vital set of proteins, all of which are components of respiratory chain complexes. Numerous mutations in mtDNA have been described in the past 5 years, and, it is, therefore, important for the clinician to keep in mind both some characteristic clinical presentations and, more importantly, some basic principles of "mitochondrial genetics," including heteroplasmy, the threshold effect, mitotic segregation, and maternal inheritance. The vast majority of mitochondrial proteins are encoded by nuclear DNA (nDNA) and have to be imported from the cytoplasm into mitochondria through a complex translocation machinery, which is also under the control of the nuclear genome. In addition, nDNA encodes several factors that control mtDNA replication, transcription, and translocation. Mitochondrial diseases due to mutations in nDNA are transmitted as mendelian traits and fall into three categories: (1) alterations of mitochondrial proteins; (2) alterations of mitochondrial protein importation; and (3) alterations of intergenomic communication. The first group of disorders can be further classified on the basis of the biochemical area affected, including defects of transport, defects of substrate utilization, defects of the Krebs cycle, defects of oxidation/phosphorylation coupling, and defects of the respiratory chain. The second group includes only few well-documented disorders but will certainly expand in the near future. The third group includes two conditions, an autosomal dominant form of progressive external ophthalmoplegia associated with multiple mtDNA deletions, and a quantitative defect of mtDNA (mtDNA depletion) causing severe infantile myopathy or hepatopathy.
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PMID:Mitochondrial encephalomyopathies. 821 79

We report a case of chronic progressive external ophthalmoplegia with pituitary hypothyroidism. This patient had complained of hearing-loss at the age of fourteen and loss of body weight at fifteen. She was examined by otorhinolaryngologists at large hospitals yearly over a period of 5-6 years, but hearing-loss remained unknown. As her ophthalmoplegia progressed (as is evident from family photographs from the age of sixteen onward), with hindsight it should have been recognized. When examined on October 11, 1991, she complained of ptosis, speech disturbance and dysphagia at the age of thirty-four. Neurological examination revealed limitation of ocular movement, bilateral ophthalmoplegia, facial muscle atrophy, and weak gag reflex. She showed muscle atrophy in her neck including both sternocleidomastoid, major and minor rhomboid, girdle and distal parts of upper and lower extremities. Muscle biopsy of her biceps demonstrated ragged-red fibers, cytochrome c oxidase (CCO) deficient fibers and deletion of mitochondrial DNA. A plain CT scan revealed bilateral periventricular lucency, and a brain MR image showed a normal sized pituitary gland but diffuse high-signal intensities in the both periventricular white matter with proton density weighted and T2-weighted axial MR image. And also her electroencephalogram showed diffuse 7 Hz slow waves in all areas and increased slow waves by hyperventilation, and all waves from I to V of the auditory brain stem response disappeared. The effect of TRH on serum TSH secretion was not evident in this patient. This case was ascertained to be chronic progressive external ophthalmoplegia with pituitary hypothyroid function.
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PMID:[A case of chronic progressive external ophthalmoplegia with pituitary hypothyroidism]. 821 98

Recent discoveries in mitochondrial clinical genetics have revealed that a broad spectrum of clinical phenotypes are associated with mutations in mitochondrial DNA. Diseases caused by mutations in mitochondrial DNA are by nature quantitative. Myoclonic epilepsy and ragged-red fiber disease are caused by a mutation in the transfer RNA gene lysine. Although everyone in a maternal lineage will harbor the same mutation, the nature and severity of the symptoms vary markedly among individuals. This variability correlates with the inherited percentage of mutations in the individual's mitochondrial DNA and the individual's age. Age-related expression of mitochondrial disease has also been demonstrated for mitochondrial DNA deletions. Although deletions that retain both origins of replication result in late-onset disease because of the progressive enrichment of the deleted mitochondrial DNA, a 10.4-kb deletion that lacks the light-strand replication origin and maintains a stable mutant percentage in both tissues and cultured cells has been discovered. This deletion is associated with adult-onset diabetes and deafness, but not with ophthalmoplegia, ptosis, or mitochondrial myopathy. Biochemically, it causes a generalized defect in mitochondrial protein synthesis and oxidative phosphorylation. The age-related decline in oxidative phosphorylation could reflect the accumulation of somatic mitochondrial DNA mutations. Inhibition of oxidative phosphorylation stimulates this accumulation. The general paradigm for mitochondrial DNA diseases may be that inherited mutations inhibit the electron transport chain. This damages the mitochondrial DNA, further reducing oxidative phosphorylation. Ultimately, oxidative phosphorylation drops below the expression threshold of cells and tissues, and clinical symptoms appear.
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PMID:Mitochondrial DNA mutations in epilepsy and neurological disease. 829 23

It has been clarified at the molecular and genetic levels that mitochondrial DNA (mt DNA) and/or nuclear DNA mutations are the cause of a group of diseases called mitochondrial cytopathies or mitochondrial myopathies. We review: (1) the characteristics of mtDNA and its inheritance, (2) the mtDNA deletions in Kearns-Sayre syndrome and chronic progressive external ophthalmoplegia, (3) the point mutations in mtDNA tRNA(Leu(UUR)) gene at positions 3,243 and 3,271 in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), (4) the mtDNA deletions and point mutations in patients with dilated or hypertrophic cardiomyopathy, and (5) the mtDNA deletions or point mutation in three pedigrees with maternally transmitted non-insulin-dependent diabetes mellitus.
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PMID:[Molecular biology of mitochondrial DNA and mutations in mitochondrial cytopathy]. 832 Aug 24


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