Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A novel G-to-A transition at nucleotide 15915 in mtDNA is described. The patient showed a combination of muscle weakness, hearing loss, mental retardation, and seizures. Muscle biopsy showed RRFs and focal COX deficiency. We sequenced all mtDNA, and found 5 novel nucleotide substitutions. Three of them were synonymous mutations, one was a missense mutation in cytochrome b gene (A-->G at nt 15422), and the last one was the 15915 mutation in tRNA(Thr) gene. We screened for the 15422 and the 15915 mutations with mismatch primers and found that one of 104 normal individuals carried the former one and none of 175 had the latter one. The 15422 mutation existed in homoplasmic states both in the patient and the normal individual, suggesting that this is a polymorphism. In contrast the 15915 mutation resided in heteroplasmic states in muscle, skin fibroblast and blood. The nucleotide substitution at nt 15915 disrupts a highly conserved base pair in anticodon stem of the tRNA(Thr). Our data suggest that the 15915 mutation is an additional mtDNA mutation responsible for mitochondrial encephalomyopathies.
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PMID:A novel mutation in the mitochondrial tRNA(Thr) gene associated with a mitochondrial encephalomyopathy. 876 14

COX deficiency is believed to be the most common defect in neonates and infants with mitochondrial diseases. To explore the causes of this group of disorders, we examined 25 mitochondrial genes (three COX subunit genes and 22 tRNA genes) and 10 nuclear COX subunit genes for disease associated mutations using PCR-SSCP and direct sequencing of polymorphic SSCP fragments. DNA from one patient with severe COX deficiency and with consanguineous parents was entirely sequenced. The patient population consisted of 21 unrelated index patients with mitochondrial disorders and predominant (n=7) or isolated (n=14) COX deficiency. We detected two distinct tRNA(Ser)(UCN) mutations, which have been recently described in single kindreds, in a subgroup of four patients with COX deficiency, deafness, myoclonic epilepsy, ataxia, and mental retardation. Besides a number of nucleotide variants, a single novel missense mutation, which may contribute to the disease phenotype, was found in the mitochondrial encoded COX 1 gene (G6480A). Mutations in nuclear encoded COX subunit genes were not detected in this study.
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PMID:A systematic mutation screen of 10 nuclear and 25 mitochondrial candidate genes in 21 patients with cytochrome c oxidase (COX) deficiency shows tRNA(Ser)(UCN) mutations in a subgroup with syndromal encephalopathy. 983 34

Cyclooxygenase-2 (COX-2) is known to be expressed in rat brain and up-regulated by ischemia. The administration of COX inhibitors before as well as soon after the ischemic insult reduces the extension of cerebral damage in rats. Overexpression of COX-2 has also been shown in the ischemic brain of adult human patients, while no information concerning COX-2 expression in neonatal ischemia is available. Intrapartum asphyxia and perinatal brain injury may result in cerebral palsy, mental retardation or epilepsy. COX-2 expression in the brain of neonates delivered after severe birth asphyxia was investigated using immunohistochemistry. Meningeal vessel walls of term and preterm babies widely expressed COX-2 immunoreactivity, as did periventricular large vessels in preterms. A number of brain cells (mature and immature cortical, periventricular and basal ganglia neurons, and oligodendrocytes of the cerebral white matter in brains from term neonates) also expressed COX-2. The present findings suggest that COX-2 may take part in enhancing neonatal brain damage via different mechanisms, such as those involving excitotoxicity and production of reactive oxygen species.
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PMID:Cyclooxygenase-2 immunoreactivity in the ischemic neonatal human brain. An autopsy study. 1184 93

Objective: To investigate the clinical features and imaging characteristics of mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS).Methods: Seventeen patients with MELAS diagnosed in the Affiliated Hospital of Xuzhou Medical University from July 2014 to August 2018 were enrolled in this study and their clinical manifestations, imaging and histopathological features were retrospectively analysed. We also discussed and summarised the related literature.Results: All of the 12 patients had seizures; stroke-like episodes in 12 cases; audio-visual impairment in 12 cases; headache in six cases; dysplasia in four cases; mental retardation in three cases; ataxia in two cases. On cranial magnetic resonance (MR) scans, the most common manifestations were in temporal-occipital-parietal lobe, cortical or subcortical areas as well as frontal lobe, thalamus, and basal ganglia showing long or equal T1 signals, long T2 signals, and hyperintense or iso-intense diffusion-weighted imaging (DWI) signals accompanied by ventricular enlargement and brain atrophy. MR spectroscopy showed that lactic acid peaks could be found in lesion sites, normal brain tissues, and cerebrospinal fluid. Muscle biopsy and genetic testing are the gold standard for diagnosing MELAS, muscle biopsy revealed COX-negative muscle fibres and SDH-stained red ragged fibres (RRF) under the sarcolemma. Mutations of mtDNA A3243G locus were common on gene testing. Improvement of mitochondrial function was observed after symptomatic and supportive treatment.Conclusion: MELAS should be considered for patients with epileptic seizures, headache, stroke-like episodes, extraocular palsy, cognitive decline and other clinical manifestations with the lesion located in the temporal-occipital-parietal lobe regardless of the distribution of blood vessels, and further examinations including muscle biopsy and gene testing should be performed to confirm the diagnosis.
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PMID:An analysis of the clinical and imaging features of mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). 3200 May 57