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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mitochondrial encephalomyopathies are usually divided into three distinct clinical subgroups: (1) mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS); (2) myoclonus epilepsy associated with ragged-red fibres (MERRF); and (3) chronic progressive external ophthalmoplegia (CPEO) including Kearns-Sayre syndrome. Large deletions of human mitochondrial DNA and a transition mutation at the mitochondrial transfer RNALys gene give rise to CPEO including Kearns-Sayre syndrome and MERRF, respectively. Here we report an A-to-G transition mutation at nucleotide pair 3,243 in the dihydrouridine loop of mitochondrial tRNA(Leu)(UUR) that is specific to patients with MELAS. Because this mutation creates an ApaI restriction site, we could perform a simple molecular diagnostic test for the disease. The mutation was present in 26 out of 31 independent MELAS patients and 1 out of 29 CPEO patients, but absent in the 5 MERRF and 50 controls tested. Southern blot analysis confirmed that the mutant DNA always coexists with the wild-type DNA (heteroplasmy).
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PMID:A mutation in the tRNA(Leu)(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies. 171 Mar 18

The A 3243 G mutation of the mitochondrial tRNA(Leu) gene was found to segregate with maternally inherited diabetes mellitus, sensorineural deafness, hypertrophic cardiomyopathy, or renal failure in a large pedigree of 35 affected members in four generations. Presenting symptoms almost consistently involved deafness and recurrent attacks of migraine-like headaches, but the clinical course of the disease varied within and across generations. The A 3243 G mutation has been previously reported in association with the mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episode syndrome (MELAS) and with diabetes mellitus and deafness. To our knowledge, however, hypertrophic cardiomyopathy is not a common feature in people with the A 3243 G mutation and renal failure has not been hitherto reported in association with this mutation. The present observation gives additional support to the variable clinical expression of mtDNA mutations in humans.
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PMID:Point mutation of the mitochondrial tRNA(Leu) gene (A 3243 G) in maternally inherited hypertrophic cardiomyopathy, diabetes mellitus, renal failure, and sensorineural deafness. 747 62

We have devised a novel method for quantitative analysis of the MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) tRNA(Leu(UUR)) mutation of mitochondrial DNA using a PCR-SSCP (polymerase chain reaction-single-strand conformation polymorphism) method, and compared the results obtained using the PCR-SSCP method with those obtained using other methods including Southern blotting, last one cycle hot PCR, and conventional PCR-RFLP (restriction fragment length polymorphism). The standard curve obtained using the PCR-SSCP method is linear, with a correlation coefficient of 0.999; it was determined that this method is more accurate than other methods for quantitative analysis. The PCR-SSCP method does not require restriction digestions, thereby avoiding potential problems of partial digestions or heteroduplex formation during PCR. The method is quite simple and should have a broad range of application for quantitation of mutant mtDNAs in various mitochondrial encephalomyopathies. We applied the method for quantitation of mutant mitochondrial DNA carrying a single base substitution in the tRNA(Leu(UUR)) gene in two autopsied cases of MELAS. In both cases, the mutant mtDNA is abundantly present (82-95%) withd little variation among tissues.
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PMID:Quantitation of heteroplasmy of mitochondrial tRNA(Leu(UUR)) gene using PCR-SSCP. 747 61

We report a patient with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) who harbored a novel missense mutation at mtDNA position 9957 in the gene specifying subunit III of cytochrome c oxidase (COX III). This T-->C transition converted Phe-251, a highly conserved amino acid in the C-terminus of the polypeptide, to Leu. The mutation, which was not present in 107 normal controls or in 57 patients with various mitochondrial diseases, was heteroplasmic in both muscle and blood of the proband and in blood from his asymptomatic mother. These results provide evidence that the MELAS clinical phenotype can be due not only to mutations in mtDNA-encoded tRNA genes, but in polypeptide-coding genes as well.
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PMID:A new mutation associated with MELAS is located in a mitochondrial DNA polypeptide-coding gene. 749 73

MELAS syndrome is a form of mitochondrial myopathy with manifestations of seizure, stroke-like syndrome, lactic acidosis, ragged red muscle fibres and mitochondrial encephalopathy. The syndrome has been reported in association with a variety of endocrine and metabolic disorders including diabetes mellitus (DM), hypothalamo-pituitary hypofunction, hypothalamic growth hormone deficiency and delayed puberty. Mitochondrial DNA (mtDNA) point mutation may be the major pathological defect. However, association of MELAS syndrome with hyperthyroidism has not previously been reported. A case is reported from Taiwan of a 32-year-old woman suffering from MELAS syndrome with associated DM and hyperthyroidism. When the latter was diagnosed in April 1988, the patient underwent subtotal thyroidectomy. There was no family history of thyroid disease. Because of repeated seizures, she had computed tomography (CT) and magnetic resonance imaging (MRI) of the brain which showed focal, low-density lesions over the cerebral hemispheres. Both serum and cerebral spinal fluid lactic acid levels were elevated. Mild elevations of serum T4 and T3 and a high titre of TSH receptor antibody were still present. Hyperglycaemia was noted during hospitalization and DM confirmed by oral glucose tolerance test. Muscle biopsy showed ragged red fibres. DNA analysis showed an A-to-G transition at the 3243rd nucleotide position of the tRNA(Leu(UUR)) gene of the mtDNA from the patient. Quantitative polymerase chain reaction (PCR) and restriction analysis revealed that about 60% of the blood mtDNA was of mutant type. The patient received antithyroid drugs for hyperthyroidism, diet control for DM and anti-epileptic drugs for seizure.
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PMID:MELAS syndrome associated with diabetes mellitus and hyperthyroidism: a case report from Taiwan. 755 21

An A to G transition at nucleotide 3,243 in the tRNA(Leu(UUR)) gene of mitochondrial DNA (mtDNA) has been suggested to be the disease-related mutation for MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes). Recently, the same mutation has also been found in several pedigrees with maternally inherited diabetes mellitus and sensorineural deafness. We report here a family showing the association of deafness and diabetes mellitus, as the predominant clinical features, with this mutation. The mutation was detected by restriction-enzyme analysis of the relevant PCR-amplified segment of the mtDNA, in two generations. In this family, it is noteworthy that two members with the mutation had some symptoms of MELAS such as short stature, seizures and mental retardation and that one had no clinical symptoms though the mtDNA mutation was identified in his blood. The findings in this family demonstrate the diversity of clinical expression of the mtDNA mutation and suggest that a combination of sensorineural deafness and diabetes mellitus is only one typical presentation of the various phenotypic features caused by the 3,243 mutation.
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PMID:[Detection of a mutation in mitochondrial DNA in a family with sensorineural deafness and diabetes mellitus as the predominant clinical features]. 756 31

Familial hemiplegic migraine (FHM) is a rare autosomal dominant disorder of unknown pathogenesis characterized by migraine and transitory hemiplegic attacks. We describe a kindred fulfilling the diagnostic criteria for FHM in which: (1) brain phosphorus magnetic resonance spectroscopy (31P-MRS) showed a reduced phosphocreatine content accompanied by high [ADP], high percentage of V/Vmax of ATP biosynthesis and decreased phosphorylation potential; (2) muscle 31P-MRS showed a reduced rate of phosphocreatine recovery after exercise; (3) blood lactate was increased after effort; (4) muscle biopsy showed, in one patient, rare ragged red fibers succinate-dehydrogenase positive and cytochrome c oxidase negative; (5) genetic analysis of muscle mitochondrial DNA did not show any of the two point mutations in the tRNA(Leu(UUR)) associated with the MELAS syndrome (Mitochondrial myopathy, Encephalopathy with Lactic Acidosis and Stroke-like episodes). The defective energy metabolism of brain and muscle found in this pedigree suggests a multisystemic disorder of mitochondrial function in this FHM pedigree.
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PMID:Abnormal brain and muscle energy metabolism shown by 31P-MRS in familial hemiplegic migraine. 760 38

We studied 22 subjects carrying the A3243G point mutation of human mitochondrial DNA (mtDNA). In 14 cases the clinical phenotype was characterized by mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), while 8 patients had chronic progressive external ophthalmoplegia (CPEO). The proportion of A3243G heteroplasmy in muscle was determined by two methods; densitometry on a diagnostic restriction-fragment length polymorphism and solid-phase mini-sequencing. We found a highly significant inverse correlation between the percentage of A3243G mutation and the specific activity of complex I, the respiratory complex with the highest number of mtDNA-encoded subunits, suggesting a direct effect of the mutation on mtDNA translation. No correlation was observed between the percentage of mutated mtDNA and the presence or absence of specific clinical features, such as stroke, ophthalmoplegia and diabetes mellitus. However, in the MELAS group the percentage of mutated mtDNA molecules was strongly correlated with the age of onset, while no such correlation was found in the CPEO group, suggesting a different time-dependent evolution of the mutation in the two groups. Finally, in contrast with other mtDNA mutations associated with ragged-red fibres (RRF), in both MELAS3243 and CPEO3243 we observed a high proportion of RRF that were positive to the histochemical reaction to cytochrome c oxidase, a morphological feature that seems to be specific for the neuromuscular phenotypes associated with mutations affecting the tRNA(Leu(UUR)) gene.
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PMID:Genotype to phenotype correlations in mitochondrial encephalomyopathies associated with the A3243G mutation of mitochondrial DNA. 764 39

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a mitochondrial disorder associated with heteroplasmic point mutations in the mitochondrial tRNA(Leu)(UUR) gene. While previous studies have shown that the MELAS mutation at nt-3243 results in impairments in mitochondrial protein synthesis and respiratory chain function, it was not clear whether these were associated with structural alterations in mature RNAs derived from transcription of the region containing the mutation. We have performed fine mapping and high-resolution. Northern analysis of RNAs from cybrids derived from two MELAS patients harboring the nt-3243 mutation. No differences in the size or steady-state levels of transcripts from the 16S rRNA, tRNA(Leu)(UUR), or ND 1 genes (which are contiguous in the mtDNA) were observed between cell lines containing mutated or wild-type mtDNAs. Therefore, it is not likely that the protein synthesis defects observed in cybrids with the MELAS-3243 mutation are directly caused by qualitative alterations in either transcription termination or processing of these mitochondrial RNAs.
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PMID:Fine mapping of mitochondrial RNAs derived from the mtDNA region containing a point mutation associated with MELAS. 768 Jan 23

We screened 214 Japanese NIDDM (non-insulin-dependent) diabetic patients with a family history of diabetes for mutations in the mitochondrial tRNA(Leu(UUR)) gene using polymerase chain reaction-restriction fragment length polymorphism and direct sequencing. Six patients were identified as having an A to G transition at position 3243 (3243 mutation), but no patients were detected with a T to C transition at position 3271, in the mitochondrial tRNA(Leu(UUR)) gene. These two mutations were not present in 85 healthy control subjects. It was disclosed that the patients' mothers were also affected by diabetes mellitus in five of the six cases. In these six affected patients, the 3243 mutation shows variable phenotypes, such as the degree of multiple organ involvement, intrafamilial and interfamilial differences in disease characteristics, and the degree of the involvement of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) phenotype. Endocrinological examinations revealed that those diabetic patients with the 3243 mutation show not only beta-cell dysfunction, but also a defect in alpha-cell function, which is considered characteristic of diabetes with the 3243 mutation. When compared with 50 selected diabetic control subjects without the 3243 mutation, whose mothers, but not fathers, were found to have diabetes, it was established statistically that those with the 3243 mutation possess the following clinical characteristics; 1) the age of diabetes onset is lower, 2) they have lean body constitutions, and 3) they are more likely to be treated with insulin than control subjects. We suggest that diabetes with the 3243 mutation possesses phenotypes distinct from those in common forms of diabetes.
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PMID:Diabetes mellitus carrying a mutation in the mitochondrial tRNA(Leu(UUR)) gene. 926 98


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