Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030552 (paresis)
 5,831 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The vascular wall weakness caused by dysplastic alterations predisposes to the spontaneous dissection of cerebral arteries. The authors hypothesized for the first time that dysplasia might be the result of mitochondrial cytopathy. To test this hypothesis, the muscle biopsy was conducted in 3 male patients, aged 30-38 years, with the spontaneous dissection of the internal carotid (2) and posterior cerebral (1) arteries. Clinically dissections manifested by ischemic stroke (2) or the peripheral paresis of the hypoglossal nerve (1). The morphological study of fresh frozen sections of muscle by modified Gomori trichrome method revealed ragged-red fibers The histochemical study showed the severe decrease of the stain on succinate dehydrogenase and cytochrome-c-oxidase as well as the focal intensive staining of peripheral regions of muscle fibers. The complex of found changes is characteristic for a mitochondrial pathology. No patients had A3243G tRNA gene mutation, the most common mutation for MELAS. The serum lactate level was elevated only in one patient. We suggest that the mitochondrial disorder occurs not only in muscle, but also in cerebral artery wall--mitochondrial arteriopathy, which predisposes to spontaneous cerebral artery dissection.
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PMID:[Mitochondrial arteriopathy as a cause of spontaneous dissection of cerebral arteries]. 2073 20

Autosomal dominant progressive external ophthalmoplegia (adPEO) is a late-onset, Mendelian mitochondrial disorder characterised by paresis of the extraocular muscles, ptosis, and skeletal-muscle restricted multiple mitochondrial DNA (mtDNA) deletions. Although dominantly inherited, pathogenic variants in POLG, TWNK and RRM2B are among the most common genetic defects of adPEO, identification of novel candidate genes and the underlying pathomechanisms remains challenging. We report the clinical, genetic and molecular investigations of a patient who presented in the seventh decade of life with PEO. Oxidative histochemistry revealed cytochrome c oxidase-deficient fibres and occasional ragged red fibres showing subsarcolemmal mitochondrial accumulation in skeletal muscle, while molecular studies identified the presence of multiple mtDNA deletions. Negative candidate screening of known nuclear genes associated with PEO prompted diagnostic exome sequencing, leading to the prioritisation of a novel heterozygous c.547G>C variant in GMPR (NM_006877.3) encoding guanosine monophosphate reductase, a cytosolic enzyme required for maintaining the cellular balance of adenine and guanine nucleotides. We show that the novel c.547G>C variant causes aberrant splicing, decreased GMPR protein levels in patient skeletal muscle, proliferating and quiescent cells, and is associated with subtle changes in nucleotide homeostasis protein levels and evidence of disturbed mtDNA maintenance in skeletal muscle. Despite confirmation of GMPR deficiency, demonstrating marked defects of mtDNA replication or nucleotide homeostasis in patient cells proved challenging. Our study proposes that GMPR is the 19th locus for PEO and highlights the complexities of uncovering disease mechanisms in late-onset PEO phenotypes.
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PMID:Identification of a novel heterozygous guanosine monophosphate reductase (GMPR) variant in a patient with a late-onset disorder of mitochondrial DNA maintenance. 3160 Aug 44