Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013362 (dysarthria)
 3,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Japanese encephalitis, an inflammatory brain disease prevalent in Southeast Asia, usually presented with fever, headache, convulsions, brain stem signs with pyramidal and extrapyramidal features, and altered sensorium. Acute transverse myelitis, as the initial manifestation of Japanese encephalitis, is an unusual manifestation and is seldom reported. We hereby report a case of 13-year-old adolescent boy who presented to us with fever and acute onset paraparesis with urinary retention initially, progressing to quadriparesis and then followed by headache and altered sensorium. Brain MRI revealed bilateral basal ganglia that were grossly swollen with vasogenic edema tracking along internal capsule and midbrain. Adjacent ventrolateral thalamus and internal capsule also showed mild abnormal intensities. Spinal screening showed abnormal cord intensities in entire cord with gross edema in cervical and conus regions. He had elevated IgM titres against JE virus in cerebrospinal fluid. The patient was treated conservatively along with intravenous methyl prednisolone for 5 days. He regained near normal power at 3 months in followup, but hesitancy, dysarthria, and slowness of movement still persisted. To conclude, a young boy presenting with ATM in an endemic region of JE, then a possibility of Japanese encephalitis, should be sought by clinicians as early use of immunomodulator shows survival benefit.
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PMID:Acute transverse myelitis (ascending myelitis) as the initial manifestation of Japanese encephalitis: a rare presentation. 2358 73

Ataxia telangiectasia (A-T) is a neurodegenerative autosomal recessive disorder with the main characteristics of progressive cerebellar degeneration, sensitivity to ionizing radiation, immunodeficiency, telangiectasia, premature aging, recurrent sinopulmonary infections, and increased risk of malignancy, especially of lymphoid origin. Ataxia Telangiectasia Mutated gene, ATM, as a causative gene for the A-T disorder, encodes the ATM protein, which plays an important role in the activation of cell-cycle checkpoints and initiation of DNA repair in response to DNA damage. Targeted next-generation sequencing (NGS) was performed on an Iranian 5-year-old boy presented with truncal and limb ataxia, telangiectasia of the eye, Hodgkin lymphoma, hyper pigmentation, total alopecia, hepatomegaly, and dysarthria. Sanger sequencing was used to confirm the candidate pathogenic variants. Computational docking was done using the HEX software to examine how this change affects the interactions of ATM with the upstream and downstream proteins. Three different variants were identified comprising two homozygous SNPs and one novel homozygous frameshift variant (c.80468047delTA, p.Thr2682ThrfsX5), which creates a stop codon in exon 57 leaving the protein truncated at its C-terminal portion. Therefore, the activation and phosphorylation of target proteins are lost. Moreover, the HEX software confirmed that the mutated protein lost its interaction with upstream and downstream proteins. The variant was classified as pathogenic based on the American College of Medical Genetics and Genomics guideline. This study expands the spectrum of ATM pathogenic variants in Iran and demonstrates the utility of targeted NGS in genetic diagnostics.
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PMID:A novel pathogenic variant in an Iranian Ataxia telangiectasia family revealed by next-generation sequencing followed by in silico analysis. 2871 42

Ataxia telangiectasia (AT) is an autosomal recessive multisystem disorder caused by mutations of ATM gene. And dystonia may develop as a late manifestation in typical AT. Here we report a novel homozygous frameshift ATM mutation (c.1402_1403delAA; p. K468Efs*18) in a 10-year-old male. The patient was diagnosed as typical AT according to clinical presentations which included progressive cerebellar ataxia, oculocutaneous telangiectasia, immune deficiency, and cerebellar atrophy. The genetic finding confirmed the diagnosis. Severe dystonia was presented in late stage of this disease. After 3 months of trihexyphenidyl treatment, the frequency of dystonia was reduced significantly. Although dystonia is not uncommon in phenotype spectrum of AT, compared with other symptoms of this syndrome, such as cerebellar ataxia and dysarthria, dystonia can be treated.
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PMID:Trihexyphenidyl for treatment of dystonia in ataxia telangiectasia: a case report. 3169 Oct 10