Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “CPEO”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources
PubMed2003

[Mitochondrial DNA mutations in patients with chronic progressive external ophthalmoplegia and Kearns-Sayre syndrome].

OBJECTIVE: Kearns-Sayre syndrome (KSS) and chronic progressive external ophthalmoplegia (CPEO) belong to neurological diseases caused by a defect in the energy-producing system of mitochondria, and are known to be associated with a deletion in the mitochondrial genome. This study was aimed to understand with greater clearness the characteristics of mitochondrial DNA (mtDNA) mutations in 11 Chinese patients with CPEO (7 cases) or KSS (4 cases). METHODS: Densitometry of the bands on Southern blot, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequencing were performed to search large scale deletions and A3243G point mutation in patients' muscle mtDNA. RESULTS: Large deletions in mtDNA were detected in 2 CPEO and 3 KSS patients, the size of deletion ranged from 3.0 kb to 8.0 kb. Moreover, mtDNA A3243G point mutation was identified in 1 KSS patient. The proportion of mutant mtDNA was 37.6%-87.0%. Direct sequencing of the PCR products revealed 5 novel large deletions not reported by others. CONCLUSION: The findings in this study being consistent with the reports by others, large scale deletions of mtDNA are frequently found in Chinese patients with KSS and CPEO. mtDNA A3243G mutation may also exist in some patients with KSS and CPEO.

Adolescent↗
PubMed2006

Investigation on mtDNA deletions and twinkle gene mutation (G1423C) in Iranian patients with chronic progressive external opthalmoplagia.

BACKGROUND: Chronic progressive external ophthalmoplagia (CPEO) is a phenotypic mitochondrial disorder that affects external ocular and skeletal muscles and is associated with a single or multiple mitochondrial DNA (mtDNA) deletions and also nuclear gene mutations. There are also some reports about the relationship between CPEO and the nuclear Twinkle gene which encodes a kind of mitochondrial protein called Twinkle. AIMS: To study the mtDNA deletions and Twinkle gene G1423C point mutation in Iranian patients with CPEO. MATERIALS AND METHODS: We collected 23 muscle samples from patients with CPEO, 9 women (mean age 34.3 years) and 14 men (36.7 years). Multiplex polymerase chain reaction (PCR) method was used to find the presence of single or multiple deletions in mtDNA. Single stranded conformational polymorphism (SSCP) and restriction fragment length polymorphism (PCR-RFLP) methods were carried out to investigate point mutation (G1423C) in the Twinkle gene in all DNA samples. RESULTS: Different sizes of mtDNA deletions were detected in 16 patients (69.6%). Each of the 5.5, 7, 7.5 and 9 kb deletions existed only in 1 patient. Common deletion (4977bp) and 8 kb deletion were detected in 5 and 3 patients respectively. Multiple deletions were also present in 4 patients. Out of 23 patients included in our study, two cases (8.7%) had Twinkle gene mutation (G1423C) and 5 patients (21.7%) did not show any deletions in mtDNA or the Twinkle gene mutation. CONCLUSION: Our study provides evidence that the investigation of mtDNA and Twinkle gene mutations in CPEO may help with early diagnosis and prevention of the disease. Patients who did not show deletions in the mtDNA or G1423C mutation in the Twinkle gene may have other mtDNA, Twinkle or nuclear gene mutations.

Adult↗
PubMed1990

Mitochondrial myopathies: divergences of genetic deletions, biochemical defects and the clinical syndromes.

Genomic Southern analysis of muscle mitochondrial (mt) DNA from 16 patients with mitochondrial myopathies was performed; 14 of 16 patients had chronic progressive external ophthalmoplegia (CPEO), while 2 patients had mitochondrial myopathies without CPEO. Eleven patients with CPEO, including 5 who exhibited the complete triad of symptoms characteristic of the Kearns-Sayre syndrome (i.e. CPEO, retinal degeneration and heart block) had heteroplasmic mtDNA with deletions ranging from 2.0 to 8.0 kb in length. There was no clear-cut correlation between the size and location of the deletions, on the one hand, and the histochemical and biochemical data or the severity of the disease, on the other.

Adolescent↗
PubMed2002

Chronic progressive external ophthalmoplegia.

Chronic progressive external ophthalmoplegia (CPEO) is a descriptive term for a heterogenous group of disorders characterized by chronic, progressive, bilateral, and usually symmetric ocular motility deficit and ptosis. Significant pain, proptosis, or pupil involvement are not features of CPEO and should prompt evaluation for alternative etiologies. Mitochondrial DNA mutations are increasingly being recognized as the etiology for CPEO syndromes. Clinicians should recognize the specific syndromes associated with CPEO, characterized by variable systemic, neurologic, or other findings. Treatment is limited, but newer therapies are being investigated.

DNA, Mitochondrial↗
PubMed1994

Central and peripheral nervous system conduction in mitochondrial myopathy with chronic progressive external ophthalmoplegia.

Involvement of the peripheral and central nervous systems in mitochondrial myopathy with chronic progressive external ophthalmoplegia (CPEO) has been demonstrated clinically and electrophysiologically. Systematic electrophysiological investigations of the peripheral and central nervous systems, particularly of cortico-spinal tract function, however, are not available. We studied peripheral and central nervous system involvement in 28 patients with histologically and biochemically proven mitochondrial CPEO by motor and sensory nerve conduction tests, by somatosensory, auditory and visual evoked potentials and, for the first time, by transcranial magnetic stimulation. Nervous system involvement could be demonstrated in 24 patients, affecting the peripheral and central nervous systems in 18 and 10 patients, respectively. Evidence of cortico-spinal tract involvement was found in 4 patients, which was clinically expected in only 2. Therefore, dysfunction of the cortico-spinal tract in mitochondrial CPEO may occur more frequently than so far assumed. Generally, electrophysiological tests serve as valuable supplements to clinical examination in patients with mitochondrial CPEO and may be especially helpful in therapeutic studies, i.e., coenzyme Q administration.

Adolescent↗
PubMed2002

External ophthalmoplegia with severe progressive multiorgan involvement associated with the mtDNA A3243G mutation.

BACKGROUND: Chronic progressive external ophthalmoplegia (CPEO) may be related to primary nuclear DNA or mitochondrial (mt)DNA mutations. The A3243G mtDNA point mutation most frequently causes mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome, but also has been associated with other phenotypes including CPEO, migraine, seizure, diabetes, and sensorineural hearing loss. CASE DESCRIPTION: We report a 38-year-old white man with seizures and progressive difficulties of infantile origin including CPEO, sensorineural hearing loss, cataracts, migraines, multiple endocrinopathy, myopathy, and cardiomyopathy. Moderate hearing loss in association with CPEO, diabetes mellitus, or migraines were noted in the proband's maternal grandmother, great aunt, mother, and three sisters, suggesting either an autosomal dominant or maternal inheritance. Detailed histological and biochemical analysis of the proband's biopsied muscle specimen revealed severe abnormalities compatible with a mitochondrial disease. MtDNA analysis excluded large-scale deletions, but revealed a heteroplasmic A to G transition at nt3243 in 56.4% and 27.4% of molecules in muscle and white blood cells, respectively. CONCLUSION: We discuss possible causes of this intrafamilial heterogeneity of phenotypes associated with the A3243G mtDNA mutation.

Adult↗
PubMed2001

The evaluation of chronic progressive external ophthalmoplegia with computerized tomography.

INTRODUCTION: Chronic progressive external ophthalmoplegia is characterised by limitation of ocular motility in all directions of gaze and ptosis. Innervational or myogenic factors were claimed to be responsible for this motility disorder. The aim of this study was to investigate the extraocular muscles in CPEO with computerized tomography in an attempt to distinguish extraocular muscle morphology caused by this disorder from that occurring in normal individuals. METHODS: Eighteen orbits from 9 patients diagnosed with CPEO were included in the study. Axial and coronal scans were obtained for CT evaluation of extraocular muscles and the dimensions of extraocular muscles were measured. The control group consisted of 40 orbits belonging to 20 individuals and, the results were compared with a student's t test. RESULTS: The thickness (the vertical dimension of vertical recti and the horizontal dimension of horizontal recti) of all rectus muscles was significantly decreased in comparison with the control group, whereas the width (the horizontal dimension of vertical recti and the vertical dimension of horizontal recti) was similar in both the diseased and normal orbits. In all the rectus muscles of the diseased orbits, the normal fusiform shape was lost and the muscles appeared as thin bands. DISCUSSION: The differentiation of CPEO from other myogenic and neurogenic disorders may present difficulty, and a cluster of criteria are required for a final diagnosis. CT has proven to be a valuable tool in assessing extraocular muscles [1, 2]. In this study, an extreme atrophy of all rectus muscles was demonstrated by means of CT. This diagnostic method may consequently contribute to a proper diagnosis of CPEO.

Adult↗
PubMed2001

Silent celiac disease in patients with childhood localization-related epilepsies.

PURPOSE: To evaluate how many patients with a clinical picture of idiopathic childhood localization-related epilepsies may also have silent celiac disease (CD). This will help determine whether investigation for CD should be restricted to those patients with childhood partial epilepsy with occipital paroxysms (CPEO) or should be extended to all patients with childhood partial epilepsy (CPE) regardless of seizure type and electroencephalographic (EEG) paroxysms. METHODS: The study group consisted of 72 patients (31 girls and 41 boys; mean age, 12.6 +/- 4.28 years; age at onset, 6.4 +/- 3.7 years) who were observed consecutively over a 5-year period and who received an initial diagnosis of idiopathic CPE. A diagnosis of CD was confirmed by using enzyme-linked immunosorbent assay (ELISA) to assess the presence of antigliadin antibodies and the immunofluorescent undirected test to assess the presence of antiendomysium antibodies. RESULTS: Twenty-five patients had CPEO, whereas the remaining 47 had CPE with centrotemporal spikes (CPEC). None of the patients with CPEC had positive antibody tests. Of the 25 patients with CPEO, two (8%) had antiendomysium immunoglobulin (Ig) A antibodies. In both of these patients, the jejunal biopsy showed atrophy of the villi and hyperplasia of the crypts, consistent with a diagnosis of CD. Brain computed tomography (CT) was normal in one of these patients and revealed occipital corticosubcortical calcifications in the other. CONCLUSIONS: Our study indicates that CD screening should be performed routinely only in patients with CPEO.

Age Factors↗
PubMed1991

Introduction of disease-related mitochondrial DNA deletions into HeLa cells lacking mitochondrial DNA results in mitochondrial dysfunction.

Mutant mitochondrial DNA with large-scale deletions (delta-mtDNA) has been frequently observed in patients with chronic progressive external ophthalmoplegia (CPEO), a subgroup of the mitochondrial encephalomyopathies. To exclude involvement of the nuclear genome in expression of the mitochondrial dysfunction characteristic of CPEO, we introduced the mtDNA of a CPEO patient into clonal mtDNA-less HeLa cells and isolated cybrid clones. Quantitation of delta-mtDNA in the cybrids revealed that delta-mtDNA was selectively propagated with higher levels of delta-mtDNA correlating with slower cellular growth rate. In these cybrid clones, translational complementation of the missing tRNAs occurred only when delta-mtDNA was less than 60% of the total mtDNA, whereas accumulation of delta-mtDNA to greater than 60% resulted in progressive inhibition of overall mitochondrial translation as well as reduction of cytochrome c oxidase activity throughout the organelle population. Because these cybrids shared the same nuclear background as HeLa cells, these results suggest that large-scale deletion mutations of mtDNA alone are sufficient for the mitochondrial dysfunction characteristic of CPEO.

Adolescent↗
PubMed2003

Executive and visuospatial deficits in patients with chronic progressive external ophthalmoplegia and Kearns-Sayre syndrome.

Although neuropsychological deficits have been reported in mitochondrial cytopathies, patients with chronic progressive external ophthalmoplegia (CPEO) or Kearns-Sayre syndrome (KSS) have not been studied systematically using a comprehensive test battery. The aim of our study was to assess the range and extent of putative cognitive dysfunction in 22 patients with CPEO or KSS, and to compare cognitive performance of patients with healthy control subjects matched for age, sex and years of education. Genetic analysis of skeletal muscle tissue from 22 patients with CPEO or KSS included screening for mitochondrial DNA (mtDNA) point mutations (3243/8344) and mtDNA deletions. All patients were examined by a neuropsychological test battery covering verbal skills, verbal and visual memory, visuo-spatial perception, visual construction, attention, abstraction and flexibility, and Quality of Life. Molecular genetic analysis of mtDNA revealed single large-scale deletions in 15 out of 22 patients and the tRNA (Leu) A3243G point mutation in two out of 22 patients. In five out of 22 patients none of the frequently encountered mtDNA mutations could be detected. Neuropsychological testing did not reveal general intellectual deterioration, but specific cognitive deficits, particularly in visual construction, attention and abstraction/flexibility. Subgroup analysis of 15 patients with mtDNA deletions showed similar results when compared with the full group. In our series of patients with CPEO or KSS neuropsychological testing did not reveal signs that would suggest general intellectual decline or dementia, but provided evidence of specific focal neuropsychological deficits, suggesting particular impairment of visuospatial perception associated to parieto-occipital lobes and executive deficits associated to the prefrontal cortex.

Adult↗
PubMed2006

Surgical treatment of blepharoptosis caused by chronic progressive external ophthalmoplegia.

UNLABELLED: Chronic progressive external ophthalmoplegia (CPEO) is a neuromyopathic disorder characterized by progressive weakness of the extraocular and levator muscles, which causes blepharoptosis and impairment of ocular motility. Because of the risk of worsening of lagophthalmos and exposure keratitis due to an associated poor Bell phenomenon or weak orbicularis function, surgical treatment of the blepharoptosis caused by CPEO is problematic. We present our experience with a case of blepharoptosis in CPEO. CASE: A 61-year-old woman presented with slowly progressive bilateral blepharoptosis. A muscle biopsy of the rectus femoris revealed mitochondrial abnormalities, which satisfied the definition of the diagnosis of CPEO as mitochondrial encephalomyopathy. The lid opening was 2 mm, with maximal frontalis contraction, the levator function was zero, and the eyeball movement was severely limited. The blow movement was about 6 mm. Combination of modest blepharoplasty and frontalis suspension using a monofilament suture was performed. The postoperative result was satisfactory, and the patient's quality of life was markedly improved.

Biopsy↗
PubMed1990

Heteroplasmy in chronic external ophthalmoplegia: clinical and molecular observations.

Chronic progressive external ophthalmoplegia (CPEO) describes a recognizable clinical syndrome frequently associated with variable dysfunction in other organ systems. Histochemical and biochemical studies suggested primary dysfunction of oxidative phosphorylation. This has recently been confirmed by demonstration of partially deleted as well as normal mitochondrial DNA--heteroplasmy--in some of these patients, most of them sporadic. In the six heteroplasmic CPEO patients that we have examined to date, the partially deleted species has been detected in all tissues tested, albeit in vastly different proportions. We report here detection of physiologically significant proportions of partially deleted mitochondrial DNA in several organs taken at autopsy from a CPEO patient with severe multisystem disease. We discuss the relationship of CPEO to several other clinical phenotypes associated with mitochondrial dysfunction, and discuss the possible implications of heteroplasmy for the development of variable phenotypes.

Child↗
PubMed1988

Chronic progressive external ophthalmoplegia. I. A quantitative histochemical study of skeletal muscles.

This study quantitates the major morphological and cytochemical changes in limb muscle biopsies from 37 patients with the syndrome of chronic progressive external ophthalmoplegia (CPEO). The aim was to assess the value of limb muscle biopsy in the diagnosis of this syndrome; to define the myopathological changes and to determine whether there were any specific clinico-pathological correlations. Patients were divided into three clinical groups--11 patients with CPEO with facial and/or limb muscle weakness; 10 with CPEO with facial and/or limb muscle weakness and a positive family history; 16 with CPEO with one or more of the following: pigmentary retinopathy, cerebellar ataxia, pyramidal signs and peripheral neuropathy. The following parameters were measured: the proportions of histochemical fibre types, the muscle fibre areas and the percentage of muscle fibres showing increased oxidative enzyme activity. Pooled results for each of the clinical categories were compared. Statistical analysis of fibre areas and the percentage of fibres with increased oxidative enzyme activity, showed that group 2 differed from the others (p less than 0.05). Patients in group 2 showed the highest incidence of type 1 fibre hypertrophy, type 2A atrophy and the lowest incidence of fibres with increased oxidative activity. Fibre type disproportions occurred in all three groups but the differences were not significant.

Biopsy↗
PubMed1992

[Clinical study on myocardial imaging with beta-methyl-p-(123I)-iodophenyl-pentadecanoic acid in patients with mitochondrial myopathy].

Myocardial imaging with beta-methyl-p-(123I)-iodophenyl-pentadecanoic acid (123I-BMIPP), a new radiopharmaceutical designed to evaluate myocardial fatty acid metabolism, was performed in 7 patients with mitochondrial myopathy to detect their myocardial damages in comparison with 201Tl myocardial imaging. These patients were divided into 4 chronic progressive external ophthalmoplegia (CPEO) cases, 2 mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) cases and 1 myoclonus epilepsy with ragged-red fibers (MERRF). In visual assessment, we observed more myocardial segments with decreased uptake of 123I-BMIPP compared to 201Tl in MELAS cases than in CPEO cases. The mean myocardial uptake of 123I-BMIPP was higher than that of 201Tl in CPEO cases. On the other hand, in MELAS and MERRF cases, the mean myocardial uptake of 123I-BMIPP was lower than that of 201Tl. Abnormal findings suggesting myocardial damages were observed in echocardiogram and/or in electrocardiogram in MELAS and MERRF cases, while no such abnormal findings were observed in CPEO cases. Along with the previously reported experimental result that the impairment of rat myocardial mitochondria decreased myocardial uptake of 125I-BMIPP, these results suggest that 123I-BMIPP may be useful to detect myocardial damages in patients with mitochondrial myopathy.

Adolescent↗
PubMed2000

Ultrastructural analysis of extraocular muscle in chronic progressive external ophthalmoplegia.

Extraocular muscles are primarily involved in many mitochondrial diseases, but no reports exist regarding the morphological appearance of the muscles in cases of long-standing ocular myopathies. For this reason, muscle samples obtained from surgery in a sporadic case of chronic progressive external ophthalmoplegia (CPEO) were used for ultrastructural investigation and molecular analysis of mitochondrial DNA. Genetic testing revealed a heteroplasmic macrodeletion of about 5.0 kilobases in length, localized between the 9570- and 14619-base pair regions. Electron microscopy revealed focal areas of both disruption and abnormality of mitochondria in only some of the muscle fibers, producing "selective vacuolization." This ultrastructural pattern was highly selective and limited to some extraocular muscle fibers, sparing all the others. The "selective damage" observed in this case of CPEO resembles that case occurring in another mitochondrial disease, Leber hereditary optic neuropathy, where damage occurs only in the papillomacular bundle of the retina, sparing peripheral axons. It is possible that some anatomical and physiological factors play a leading role in both Leber hereditary optic neuropathy and ocular myopathies. The ultrastructural aspect herein observed needs to be further investigated to better understand whether a particular muscle fiber type is the target of mitochondrial impairment in CPEO.

Base Sequence↗
PubMed1996

Reduced brain stem excitability in mitochondrial myopathy: evidence for early detection with blink reflex habituation studies.

Blink reflex (BR) was studied in 17 patients with histochemically and genetically confirmed mitochondrial myopathy (MM). Fourteen patients had chronic progressive external ophthalmoplegia (CPEO) associated with a mild to moderate craniosomatic myopathy without any symptoms or signs of central nervous system (CNS) involvement, 2 myoclonic epilepsy with ragged red fibers syndrome, and 1 Kearns-Sayre syndrome. The mean latencies of the early (R1) and late (R2) responses were prolonged (P < 0.01 and P < 0.001, respectively), and the corresponding amplitudes decreased (P < 0.001). Increased habituation of the reflex was clearly observed in 10 out of 14 patients tested (71.4%), 9 of whom presented CPEO. These findings suggest that the brain stem reticular network is in a state of basal inhibition which is presumably due to a subclinical impairment of the cerebral cellular metabolism. Multimodal evoked potentials revealed abnormalities suggestive of CNS involvement in 7 out of 17 patients (41.2%), 4 of whom had CPEO. These observations document the validity of BR in detecting clinically silent brain stem impairment in patients with apparently pure MM and provide important clues for a further understanding of the underlying pathophysiology.

Adolescent↗
PubMed1999

Quantitative near-infrared spectroscopy discriminates between mitochondrial myopathies and normal muscle.

Five patients with chronic progressive external ophthalmoplegia (CPEO) and 27 healthy controls were examined by near-infrared spectroscopy (NIRS) for the noninvasive and direct quantitative measurement of muscle oxygen consumption and forearm blood flow. NIRS measurements were obtained in rest and during static isometric handgrip exercise at 10% of the maximum voluntary contraction (MVC) force. A significantly decreased oxygen consumption at rest as well as during exercise was found in patients with CPEO. Our results suggest that NIRS is able to discriminate between CPEO patients and healthy controls, which makes NIRS a valuable tool in the diagnostic workup of patients suspected to have a mitochondrial myopathy.

Adult↗
PubMed2003

Oxidative capacity correlates with muscle mutation load in mitochondrial myopathy.

The purpose of this study was to investigate the correlation between the level of mutated mitochondrial DNA in muscle and oxidative capacity in 24 patients with mitochondrial myopathy (MM). Maximal oxygen uptake (VO(2max)), workload (W(max)), and venous plasma lactate levels were measured during an incremental cycle test to exhaustion in 17 patients with point mutations of mtDNA and in seven with single, large-scale deletions of mtDNA (chronic progressive external ophthalmoplegia [CPEO]). Results were compared with those in 25 healthy matched subjects. The mutation load in MM patients was 67 +/- 5% (range, 29 - 99%). VO(2max) and W(max) correlated with percentage of heteroplasmy (r > 0.82; p < 0.005) and were lower in patients versus healthy subjects (p < 0.000005). Exercise-induced peak increases in heart rate, ventilation, and resting plasma lactate levels correlated with muscle mutation load (r > 0.71; p < 0.005). Exercise-induced increases in plasma lactate correlated with muscle mutation load in CPEO patients (r = 0.95; p < 0.005). Impaired oxidative capacity and ragged red muscle fibers were found in CPEO and 3243A-->G patients with mutation loads as low as 45 and 57%, respectively. The study indicates that oxidative capacity correlates directly with skeletal muscle mutation load in MM patients, and that the mutation threshold level for impaired oxidative metabolism in MM patients is lower than found in in vitro studies.

Adult↗