Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033377 (prolapse)
 11,717 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leigh syndrome is a subacute necrotising encephalomyopathy proven by post-mortem analysis of brain tissue showing spongiform lesions with vacuolation of the neuropil followed by demyelination, gliosis and capillary proliferation caused by mutations in one of over 75 different genes, including nuclear- and mitochondrial-encoded genes, most of which are associated with mitochondrial respiratory chain function. In this study, we report a patient with suspected Leigh syndrome presenting with seizures, ptosis, scoliosis, dystonia, symmetrical putaminal abnormalities and a lactate peak on brain MRS, but showing normal MRC enzymology in muscle and liver, thereby complicating the diagnosis. Whole exome sequencing uncovered compound heterozygous mutations in NADH dehydrogenase (ubiquinone) flavoprotein 1 gene (NDUFV1), c.1162+4A>C (NM_007103.3), resulting in skipping of exon 8, and c.640G>A, causing the amino acid substitution p.Glu214Lys, both of which have previously been reported in a patient with complex I deficiency. Patient fibroblasts showed a significant reduction in NDUFV1 protein expression, decreased complex CI and complex IV assembly and consequential reductions in the enzymatic activities of both complexes by 38% and 67%, respectively. The pathogenic effect of these variations was further confirmed by immunoblot analysis of subunits for MRC enzyme complexes in patient muscle, liver and fibroblast where we observed 90%, 60% and 95% reduction in complex CI, respectively. Together these studies highlight the importance of a comprehensive, multipronged approach to the laboratory evaluation of patients with suspected Leigh syndrome.
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PMID:Whole Exome Sequencing Identifies the Genetic Basis of Late-Onset Leigh Syndrome in a Patient with MRI but Little Biochemical Evidence of a Mitochondrial Disorder. 2734 48

A 30-year-old woman with congenital vocal cord paralysis presented for evaluation of fatigable proximal upper limb weakness and difficulty maintaining the neck erect. Neurologic examination showed bilateral asymmetric eyelid ptosis, mild weakness (MRC 4/5), and atrophy of neck extensors and shoulder girdle muscles, whereas lower limb muscle strength was normal. Repetitive nerve stimulation revealed decremental responses in orbicularis oculis and trapezius. Needle electromyography demonstrated myopathic changes in proximal and paraspinal muscles. Acetylcholine receptor and muscle skeletal receptor tyrosine kinase (MuSK) antibodies, creatine kinase (CK), and lactate were negative or normal. Next-generation sequencing detected two heterozygous variants in the MUSK gene. One variant, c.79+2T>G, is a known pathogenic variant, and the other, c.2165T>C (p.V722A), is a novel missense variant, predicted to be pathogenic by in silico analysis. The two variants were proven to be in trans. This case expands the clinical and molecular spectrum of MuSK congenital myasthenic syndromes.
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PMID:Congenital Vocal Cord Paralysis and Late-Onset Limb-Girdle Weakness in MuSK-Congenital Myasthenic Syndrome. 3192 Sep 24