Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dehydration is one of the ten most frequent diagnoses responsible for the hospital admission of elderly in the United States. It is associated with increased mortality, morbidity and an estimated cost of 1.14 billion per year (Xiao et al., 2004; Schlanger et al., 2010; Pretorius et al., 2013; Frangeskou et al., 2015). Older individuals are predisposed to dehydration encephalopathy as a result of decreased total body water (TBW) and diminished sensation of thirst. We hypothesize that thirst blunting in older individuals is the result of a defective microRNA-6842-3p failing to silence the expression of the vesicular GABA transporters (VGAT) and alpha 7 cholinergic nicotinic receptors in the subfornical organ (SFO) of the hypothalamus. We hypothesize further that resultant dehydration facilitates protein misfolding and aggregation, predisposing to neurocognitive disorders. We completed a search of predicted microRNA targets, utilizing the public domain tool miRDB and found that microRNA-6842-3p modulates the SLC6A1 and CHRNA7 genes both of which were previously hypothesized to inhibit the thirst sensation by their action on SFO. The primary aim of this article is to answer two questions: Can prevention and correction of dehydration in elderly lower age-related cognitive deterioration? Can exosomal miR-6842 in the peripheral blood predict dehydration encephalopathy in elderly?
...
PMID:Dehydration and Cognition in Geriatrics: A Hydromolecular Hypothesis. 2725 43

SLC6A1 is associated with an autosomal dominant early-onset seizure and epileptic encephalopathy associated with intellectual disability. We present a 2-yr-old girl with developmental delay and epilepsy, using a new computational filtering impact score to show the patient's variant ranks with other pathogenic variants. Genomic studies within the patient revealed a G443D variant of uncertain significance. Structural and evolutionary assessments establish this variant as a loss of function to the protein. Compiled metrics through our custom tools on sequence, structure, and protein dynamics combined with PolyPhen-2, PROVEAN, SIFT, and Align-GVGD reveal this variant to rank in the top functional outcome changes relative to gnomAD, TOPMed, and ClinVar variants known to date. The patient was resistant to multiple epileptic drugs, finally finding that valproic acid controls the seizures. This is consistent with additional groups studying SLC6A1 variants within patients.
 ...
PMID:SLC6A1 G443D associated with developmental delay and epilepsy. 3266 Sep 67