Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042571 (vertigo)
 7,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors report an autosomal dominant episodic ataxia that is clinically distinct from the other episodic ataxias. Vestibular ataxia, vertigo, tinnitus, and interictal myokymia are prominent; attacks are diminished by acetazolamide. Linkage analyses of markers flanking the EA1 and EA2 loci demonstrate genetic exclusion from the other autosomal dominant episodic ataxias. The authors suggest EA3 for periodic vestibulocerebellar ataxia and EA4 for the disorder described here.
 ...
PMID:An autosomal dominant disorder with episodic ataxia, vertigo, and tinnitus. 1167

Episodic ataxias (EAs) are rare channelopathies characterized by recurrent ataxia and vertigo, having eight subtypes. Mutated genes were found in four of these eight subtypes (EA1, EA2, EA5, and EA6). To date, only four missense mutations in the Solute Carrier Family 1 Member 3 gene (SLC1A3) have been reported to cause EA6. SLC1A3 encodes excitatory amino-acid transporter 1, which is a trimeric transmembrane protein responsible for glutamate transport in the synaptic cleft. In this study, we found a novel missense mutation, c.383T>G (p.Met128Arg) in SLC1A3, in an EA patient by whole-exome sequencing. The modeled structural analysis suggested that p.Met128Arg may affect the hydrophobic transmembrane environment and protein function. Analysis of the pathogenicity of all mutations found in SLC1A3 to date using multiple prediction tools showed some advantage of using the Mendelian Clinically Applicable Pathogenicity (M-CAP) score. Various types of SLC1A3 variants, including nonsense mutations and indels, in the ExAC database suggest that the loss-of-function mechanism by SLC1A3 mutations is unlikely in EA6. The current mutation (p.Med128Arg) presumably has a gain-of-function effect as described in a previous report.
 ...
PMID:A novel mutation in SLC1A3 causes episodic ataxia. 2920 48

Episodic ataxias (EAs) are characterized by recurrent, discrete episodes of vertigo and ataxia. EA1 and EA2 are the two most common forms. In the interictal interval, myokymia is typically present in EA1, whereas EA2 patients present with interictal nystagmus. Specific pharmacological therapies are available for EA1 and especially EA2. We briefly discuss the case of an Italian young man with EA2, with a novel de novo CACNA1A mutation, who in our opinion is particularly illustrative for introducing the therapeutic approach. Acetazolamide could fully suppress EA episodes in our patient. We also provide a perspective review of the topic. 4-Aminopyridine is another valid treatment option. For EA1 (and for rarer EAs), the therapeutic possibilities are more limited. Carbamazepine is probably the treatment of choice for EA1, but the optimal treatment plan is unknown. A better understanding of the molecular processes involved in the mediation of EAs will lead to more specific and efficacious therapies for this still elusive group of disorders.
 ...
PMID:Therapy of episodic ataxias: case report and review of the literature. 3089 Oct 74