Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Type 2 episodic ataxia (EA2) is the most common subtype among a group of rare hereditary syndromes characterized by recurrent attacks of ataxia. More than 60 mutations and several gene rearrangements due to large deletions in CACNA1A gene have been reported so far for the cause of EA2. Because CACNA1A gene is a large gene containing 47 exons and there is no hot spot mutation, direct sequencing will be a challenge in clinical genetic testing. In this study, we used next generation sequencing technology to identify a novel nonsense mutation of CACNA1A (p.Tyr1957Ter, NP_001120693.1) resulting in truncated protein without 305 amino acids in the c-terminus. Sanger sequencing confirmed the heterozygous mutation of CACNA1A in a Chinese family with 11 affected individuals. Affected individuals experienced recurrent attacks with or without nystagmus, dysarthria, seizure, myokymia, dystonia, weakness, blurred vision, visual field defects, diplopia, migraine, dizziness, nausea and vomiting, sweating and abdominal pain. This is the first report of EA2 in a Chinese family that carries a novel mutation in CACNA1A gene and had abdominal pain as a novel phenotype associated with EA2.
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PMID:Identification of a novel nonsense mutation p.Tyr1957Ter of CACNA1A in a Chinese family with episodic ataxia 2. 2344 Nov 82

Episodic ataxia type 2 (EA2, MIM#108500) is the most common form of EA and an autosomal-dominant inherited disorder characterized by paroxysmal episodes of ataxia. The disease causative gene CACNA1A encodes for the alpha 1A subunit of the voltage-gated P/Q-type calcium channel. We report on a family with a novel mutation in the CACNA1A gene. The clinical symptoms within the family varied from the typical clinical presentation of EA2 with dysarthria, gait ataxia and oculomotor symptoms to migraine and dystonia. A novel nonsense mutation of the CACNA1A gene was identified in all affected family members and is most likely the disease causing molecular defect. The pharmacological treatment with acetazolamide (AAA) was successful in three family members so far. Treatment with AAA led to a reduction of migraine attacks and an improvement of the dystonia. This relationship confirmed the hypothesis that this novel mutation results in a heterogeneous phenotype and confutes the coincidence with common migraine. Dystonia is potentially included as a further part of the phenotype spectrum of CACNA1A gene mutations.
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PMID:Novel frameshift mutation in the CACNA1A gene causing a mixed phenotype of episodic ataxia and familiar hemiplegic migraine. 2546 64