Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0162671 (MELAS)
 587 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 3 of 40 MELAS patients, a new common mutation, a T-to-C transition at nucleotide position 3271 in the mitochondrial tRNA(Leu(UUR] gene was recognized and was very near to the most common mutation site at 3243. With a simple detection method using polymerase chain reaction with a mismatch primer, none of 46 patients with other mitochondrial diseases and 50 controls had this mutation.
 ...
PMID:A new mtDNA mutation associated with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). 193 47

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.
 ...
PMID:Quantitation of heteroplasmy of mitochondrial tRNA(Leu(UUR)) gene using PCR-SSCP. 747 61

A new point mutation at nucleotide pair 3291 in the mitochondrial tRNA-Leu(UUR) gene was found in a Japanese MELAS patient. The nucleotides at the mutated site were evolutionarily invariant from humans through sea urchins. The mutant genomes were detected in a heteroplasmic fashion in muscle and blood cells of the proband by means of PCR-RFLP. Among 46 MELAS, 5 MERRF, 23 CPEO and 55 normal controls examined, this is the only patient with the mutation. This is the third mutation associated with MELAS in addition to nucleotides at 3243 and 3271. All three mutations occurred within the tRNA-Lue(UUR) region indicating that the tRNA alteration is responsible for the MELAS phenotype.
 ...
PMID:A new point mutation at nucleotide pair 3291 of the mitochondrial tRNA(Leu(UUR)) gene in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). 752 Feb 41

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.
 ...
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.
 ...
PMID:[Detection of a mutation in mitochondrial DNA in a family with sensorineural deafness and diabetes mellitus as the predominant clinical features]. 756 31

The recent development of cellular models of mitochondrial DNA-linked diseases by transfer of patient-derived mitochondria into human mtDNA-less (rho o) cells has provided a valuable tool for investigating the complementation and segregation of mtDNA mutations. In transformants carrying in heteroplasmic form the mitochondrial tRNA(Lys) gene 8344 mutation or tRNA(Leu(UUR)) gene 3243 mutation associated, respectively, with the MERRF or the MELAS encephalomyopathy, full protection of the cells against the protein synthesis and respiration defects caused by the mutations was observed when the wild-type mtDNA exceeded 10% of the total complement. In the MERRF transformants, the protective effect of wild-type mtDNA was shown to involve interactions of the mutant and wild-type gene products, probably coexisting within the same organelle from the time of the mutation event. In striking contrast, in experiments in which two mtDNAs carrying either the MERRF or the MELAS mutation were sequentially introduced within distinct organelles into the same rho o cells, no evidence of cooperation between their products was observed. These results pointed to the phenotypic independence of the two genomes. A similar conclusion was reached in experiments in which a chloramphenicol (CAP) resistance-conferring mtDNA mutation was introduced into CAP-sensitive cells. In the area of segregation of mtDNA mutations, in unstable heteroplasmic MELAS transformants, observations were made which pointed to a replicative advantage of mutant molecules, leading to a rapid shift of the genome towards the mutant type. These results are consistent with a model in which the mitochondrion, rather than the mtDNA molecule, is the segregating unit.
 ...
PMID:Complementation and segregation behavior of disease-causing mitochondrial DNA mutations in cellular model systems. 759 15

MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes), a maternally inherited mitochondrial disorder, has been associated with an A-->G transition at nucleotide 3243 and a T-->C transition at nucleotide 3271, both in the mitochondrial tRNA(Leu(UUR)) gene. We transferred mitochondria harboring these mutations into human cells lacking endogenous mtDNA (rho o cells), and analyzed the resulting transmitochondrial cytoplasmic hybrid (cybrid) cell lines for the relationship of genotype to phenotype. Cybrids containing high levels of mutated genomes showed decreased rates of synthesis of mitochondrial translation products, reduced respiratory chain function, and increased amounts of a novel unprocessed RNA species (RNA 19). Overall effects on mitochondrial functions were more severe for the MELAS 3243 cybrids as compared to the MELAS 3271 cybrids. These data, combined with our previous observations, suggest that RNA 19 may play an important, but as yet uncharacterized, role in the pathogenesis of this mitochondrial disorder.
 ...
PMID:Analysis of cybrids harboring MELAS mutations in the mitochondrial tRNA(Leu(UUR)) gene. 760 12

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.
 ...
PMID:Abnormal brain and muscle energy metabolism shown by 31P-MRS in familial hemiplegic migraine. 760 38

We found a new point mutation in the mitochondrial tRNA(Ser(UCN)) gene in a family with MERRF/MELAS overlap syndrome by screening for heteroplasmy by means of chemical cleavage of mismatch (CCM). Our strategy was based on the previous observations that most pathogenic mtDNA mutations in mitochondrial encephalomyopathies are heteroplasmic, whereas almost all neutral mitochondrial polymorphisms are homoplasmic. CCM followed by nucleotide sequencing of the corresponding region of the mitochondrial genome revealed a heteroplasmic mutation at nt 7512 in the tRNA(Ser(UCN)) gene. The 7512 (T to C) mutation disrupts a highly conserved base pair in the acceptor stem, and this mutation was not found in any of 120 normal controls, or in 43 patients with mitochondrial diseases. The proportion of the mutant mtDNA was 93% in muscle, 76 and 87% in the blood of the patients. A family member without apparent neuromuscular symptoms carried less mutant mtDNA. These findings support the view that this mutation is pathogenic in this family. Detection of heteroplasmy by CCM is an efficient means of screening pathogenic mtDNA point mutations.
 ...
PMID:A novel point mutation in the mitochondrial tRNA(Ser(UCN)) gene detected in a family with MERRF/MELAS overlap syndrome. 766 57

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.
 ...
PMID:Diabetes mellitus carrying a mutation in the mitochondrial tRNA(Leu(UUR)) gene. 926 98


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>