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

Mitochondriopathies (MCPs) that reach adult age not only manifest in the central and peripheral nervous systems, eyes, ears, and dermis, but also in visceral organs, such as endocrine organs, heart, liver, guts, kidneys and blood. Visceral manifestations occur as part of a multisystem involvement or rarely as single organ affection. Endocrinological abnormalities are found in the MELAS, MERRF , KSS , MID and DID MOAD syndromes. Cardiac involvement occurs in the MELAS, MERRF , KSS , CPEO, LHO N, NARP, and Leigh syndromes. Gastrointestinal manifestations are common in the MERRF , MNGI E, DID MOAD, and Leigh syndromes. Mitochondrial syndromes with renal manifestations are the KSS , Pearson, DID MOAD, and Leigh syndromes. The haematopoetic system is affected in the KSS , MERRF , and Leigh syndromes. In addition, visceral manifestations are found in many nonsyndromic MCPs. Although there is no causal therapy for MCPs, adequate symptomatic therapy, particularly of visceral manifestations, markedly improves quality of life and prognosis of these still often neglected or overlooked disorders.
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PMID:Overview on visceral manifestations of mitochondrial disorders. 1654 58

Ocular complications are common in the mitochondrial cytopathies and include optic atrophy and retinal degeneration. We retrospectively reviewed 80 patients with nonsyndromic mitochondrial cytopathies (ie, not Kearns-Sayre syndrome, myoclonus epilepsy associated with ragged red fibers [MERRF], mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes [MELAS], neuropathy ataxia and retinitis pigmentosa, Leigh disease, maternally inherited diabetes and deafness, and myoneurogastrointestinal disorder and encephalopathy) and found 10 cases of optic nerve hypoplasia. Optic nerve hypoplasia occurs in at least 12% of patients with nonsyndromic mitochondrial cytopathies. Although the exact pathogenesis of optic nerve hypoplasia in the context of mitochondrial cytopathy is unknown, we postulate that it is the result of excessive apoptosis during embryonic ganglion cell and/or axonal development from abnormal mitochondrial function and cellular energy metabolism.
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PMID:Association of optic nerve hypoplasia with mitochondrial cytopathies. 1709 61

A growing number of mutations in mitochondrial (mt) tRNA genes have been found to associate with human mitochondrial diseases. Our previous analysis of mutant mt tRNAs isolated from cells derived from patients with mitochondrial diseases revealed the lack of a post-transcriptional taurine-modification at the anticodon wobble uridine in two mt tRNAs bearing typical pathogenic mutations: mt tRNA(Leu(UUR)) with either the MELAS 3243 or 3271 mutation and mt tRNA(Lys) with the MERRF 8344 mutation. We here summarize our recent studies that clarify the molecular basis of the defective mitochondrial translation caused by this wobble modification deficiency. The MERRF mt tRNA(Lys) lacking the wobble modification cannot translate either of its codons (AAA and AAG), while the translational activity of MELAS mt tRNA(Leu(UUR)) lacking wobble modification is more depressed in decoding of UUG codon than UUA codon. These findings suggest that the wobble modification deficiency plays a primary role in the molecular pathogenesis of the MELAS and MERRF mitochondrial diseases.
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PMID:Human mitochondrial diseases associated with tRNA wobble modification deficiency. 1713 41

To investigate the spectrum of common mitochondrial mutations in Northern China during the years of 2000-2005, 552 patients of mitochondrial encephalomyopathies clinically diagnosed as MELAS, MERRF or Leigh's syndrome, 14 cases of LHON and 46 cases of aminoglycoside induced deafness along with their family members, accepted routine point mutation tests at nucleotide positions 3243, 8344, 8993, 11778 or 1555 in mitochondrial genome. PCR-RFLP analysis, site-specific PCR and PCR-sequencing methods were used to identify the mutations. Fifty-seven cases with A3243G mutation, 4 cases with A8344G, 2 cases with T8993C and 1 case with T8993G were identified from the 552 encephalomyopathy patients. In addition, one case with G11778A was found from the 14 cases of LHON, and 5 cases with A1555G from the 46 cases of aminoglycoside ototoxicity patients. Additional screening for T8356G and T3271C merely had limited significance for the diagnosis of MERRF and MELAS. Differential diagnosis among mitochondrial encephalomyopathies was often complicated due to many similar clinical manifestations. For A3243G mutation, the proportion of mutant mtDNA was not related to severity of the disease but to the age of onset.
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PMID:Screening of common mitochondrial mutations in Chinese patients with mitochondrial encephalomyopathies. 1727 42

The mitochondrial tRNA(Leu(UUR)) gene (MTTL) is a hot spot for pathogenic mutations that are associated with mitochondrial diseases with various clinical features. Among these mutations, the A3243G mutation was associated with various types of mitochondrial multisystem disorders, such as MIDD, MELAS, MERRF, PEO, hypertrophic cardiomyopathy, and a subtype of Leigh syndrome. We screened 128 Tunisian patients for the A3243G mutation in the mitochondrial tRNA(Leu(UUR)) gene. This screening was carried out using PCR-RFLP with the restriction endonuclease ApaI. None of the 128 patients or the 100 controls tested were found to carry the mitochondrial A3243G mutation in the tRNA(Leu(UUR)) gene in homoplasmic or heteroplasmic form. After direct sequencing of the entire mitochondrial tRNA(Leu(UUR)) gene and a part of the mitochondrial NADH dehydrogenase 1, we found neither mutations nor polymorphisms in the MTTL1 gene in the tested patients and controls, and we confirmed the absence of the A3243G mutation in this gene. We also found a T3396C transition in the ND1 gene in one family with NSHL which was absent in the other patients and in 100 controls. Neither polymorphisms nor other mutations were found in the mitochondrial tRNA(Leu(UUR)) gene in the tested patients.
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PMID:Mutational analysis of the mitochondrial tRNALeu(UUR) gene in Tunisian patients with mitochondrial diseases. 1733 24

Non-syndromic deafness can be caused by mutations in both nuclear and mitochondrial genes. More than 50 nuclear genes have been shown to be involved in non-syndromic hearing loss, but mutations in mitochondrial DNA (mtDNA) might also cause hearing impairment. As mitochondria are responsible for oxidative phosphorylation, the primary energy-producing system in all eukaryotic cells, mitochondrial dysfunction has pleiotropic effects. Many mutations in mtDNA can lead to multisystem disorders, such as Kearns-Sayre syndrome, NARP, MELAS, or MERRF syndromes, the presentation of which may include hearing loss. A more specific association of mitochondrially inherited deafness and diabetes known as MIDD syndrome can be caused by a limited number of specific mitochondrial mutations. In addition, several rare mutations in the mitochondrial MTTS1 and MTRNR1 genes have been found to be responsible for non-syndromic hearing loss. The most frequent form of non-syndromic deafness is presbyacusis, affecting more than 50% of the elderly. This age-related hearing loss is a paradigm for multifactorial inheritance, involving a multitude of inherited and acquired mutations in the nuclear and mitochondrial genomes, each with a low penetrance, in complex interplay with environmental factors, such as ototoxic medication, that accumulate with age. This study reviews the different mitochondrial mutations, leading to syndromic and especially non-syndromic deafness.
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PMID:Mitochondrial deafness. 1748 42

The term "mitochondrial diseases" (MD) refers to a group of disorders related to respiratory chain dysfunction. Clinical features are usually extremely heterogeneous because MD may involve several tissues with different degrees of severity. Muscle and brain are mostly affected, probably because of their high dependence on oxidative metabolism. Muscle can be the only affected tissue or involved as a part of a multi-system disease; ragged red fibers, accumulation of structurally altered mitochondria and cytochrome-c-oxidase (COX) negative fibers are the main pathological features. In mitochondrial encephalopathies, central nervous system (CNS) structures are affected according to different patterns of distribution and severity. Characteristic lesions are neuronal loss, vasculo-necrotic changes, gliosis, demyelination and spongy degeneration. In accordance with either grey matter or white matter involvement two main groups of diseases may be distinguished. Neuronal loss and vasculo-necrotic multifocal lesions are the common features of grey matter involvement; demyelination and spongy degeneration occur when white matter is affected, often associated with less severe lesions of the grey structures. Grey matter lesions are prevalent in MERRF, MELAS, Alpers and Leigh syndromes. White matter involvement is always seen in Kearns-Sayre syndrome and was recently described in mtDNA depletion syndrome linked to dGK mutations and in the rare conditions associated with complex I and II deficiency. In this review we describe the main histopathological features of muscle and CNS lesions in mitochondrial diseases.
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PMID:Neuropathology of mitochondrial diseases. 1754 38

Mitochondrial encephalopathies are a group of diseases that have as their pathogenic basis an alteration of the mitochondrial DNA (mtDNA). The MELAS phenotype (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) has been related to mutation A3243G in approximately 80% of the cases reported. MERRF (epilepsy myoclonus with ragged red fibers) has been related to mutation A8344G and A8566G of tRNA Lys. We report the case of a 7 months-old female with early clinical signs of encephalopathy associated to the A3243G mutation. Laboratory tests showed lactic acidosis and the EEG pattern was compatible with an encephalopathic process. The infant was treated with ACTH during one month, with clinical and electroencephalographic improvements. Currently, she is receiving treatment with B-vitamins, L-Carnitine and urinary alkalizing agents. It is concluded that an analysis of mtDNA must be made in infants who present convulsions, delay in their psychomotor development, lactic acidosis and an EEG pattern compatible with an encephalopathy, to rule out a mitochondrial disease.
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PMID:[Infantile encephalopathy associated with the MELAS A3243G mutation. Case report]. 1759 46

The impact of point mutations in mitochondrial tRNA genes on the amount and stability of respiratory chain complexes and ATP synthase (OXPHOS) has been broadly characterized in cultured skin fibroblasts, skeletal muscle samples, and mitochondrial cybrids. However, less is known about how these mutations affect other tissues, especially the brain. We have compared OXPHOS protein deficiency patterns in skeletal muscle mitochondria of patients with Leigh (8363G>A), MERRF (8344A>G), and MELAS (3243A>G) syndromes. Both mutations that affect mt-tRNA(Lys) (8363G>A, 8344A>G) resulted in severe combined deficiency of complexes I and IV, compared to an isolated severe defect of complex I in the 3243A>G sample (mt-tRNA(LeuUUR). Furthermore, we compared obtained patterns with those found in the heart, frontal cortex, and liver of 8363G>A and 3243A>G patients. In the frontal cortex mitochondria of both patients, the patterns of OXPHOS deficiencies differed substantially from those observed in other tissues, and this difference was particularly striking for ATP synthase. Surprisingly, in the frontal cortex of the 3243A>G patient, whose ATP synthase level was below the detection limit, the assembly of complex IV, as inferred from 2D-PAGE immunoblotting, appeared to be hindered by some factor other than the availability of mtDNA-encoded subunits.
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PMID:The impact of mitochondrial tRNA mutations on the amount of ATP synthase differs in the brain compared to other tissues. 1831 67

We developed an oligonucleotide biochip for synchronous multiplex detection of 31 known mitochondrial DNA mutations associated with MELAS (Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) and MERRF (Myoclonic epilepsy with ragged red fibers). Allele-specific oligonucleotide probes were covalently immobilized on aldehyde modified glass slides, and then hybridized with Cy5-labled DNA fragments amplified from sample DNAs by a multiplex asymmetric PCR (MAP) method. Five patients with MELAS, 5 patients with MERRF and 20 healthy controls were investigated using the oligonucleotide biochip. The results showed that all the cases with MELAS had an A3243G mutation in the MT-TL1 gene. In the MERRF group, 4 cases were found to be an A8344G mutation and 1 case was a T8356C mutation, and both mutations were in the MT-TK gene. In the healthy controls, none of the 31 related mutations was found. The results of the DNA biochip were consistent with those by DNA sequencing. Clearly, the DNA biochip combined with MAP method would become a valuable tool in multiplex detecting of the point mutations in mtDNA leading to MELAS and/or MERRF syndrome. Moreover, this biochip format could be modified to extend to the screening scope of SNPs for any other human mitochondrial diseases.
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PMID:[Development of a DNA biochip for detection of known mtDNA mutations associated with MELAS and MERRF syndromes.]. 1893 Aug 87


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