Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007758 (cerebellar ataxia)
 3,609 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Episodic ataxia (EA) is a rare, disabling condition of autosomal dominant inheritance, but it is not a distinct clinical entity. Synonyms are familial periodic ataxia or hereditary paroxysmal cerebellar ataxia. Family members have a similar clinical syndrome; however, the syndrome varies considerably from family to family. At least two groups of disorders have been separated clinically: (1) episodic ataxia type 1 (EA-1), which manifests without vertigo and is associated with 'interictal' myokymia, and (2) episodic ataxia type 2 (EA-2), which often manifests with vertigo and is associated with 'interictal' nystagmus. EA-1 and EA-2 have been identified as channelopathies. EA-1 is due to different heterozygous missense point mutations in a voltage-gated (delayed rectifier) potassium channel gene (KCNA1/Kv1.1) on chromosome 12p13, whereas EA-2 is caused by mutations of the cerebral P/Q-type calcium channel alpha 1 subunit gene CACNL1A4 localized on chromosome 19p, which is highly expressed in the cerebellum. The diagnosis of EA-1 and EA-2 is important, since they can be easily treated and are often mislabeled. As effective as acetazolamide is in preventing attacks, prospective studies still have to prove whether it can prevent progressive ataxia in EA-2 or even improve chronic cerebellar deficits.
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PMID:Episodic ataxia type 1 and 2 (familial periodic ataxia/vertigo). 939 Aug 41

Inherited ataxias are a heterogeneous group of disorders characterized by autosomal dominant and recessive inheritance. Recent advances in genetic research have resulted in an improved comprehension of their clinical presentation. Autosomal dominant cerebellar ataxias (ADCAs) include spinocerebellar ataxias (SCAs) and dentatorubral-pallidoluysian atrophy (DRPLA); six of these have been found to be trinucleotide repeat disorders. Episodic ataxia, types 1 and 2, are at present recognized to be channelopathies, caused by point mutations. Friedreich's ataxia (FA) which is an autosomal recessive disorder, resulting from a a unique trinucleotide repeat, is now recognized to have a wide age of onset and clinical spectrum. Ataxia-telangiectasia (AT), also an autosomal recessive cerebellar ataxia, is characterized by immunodeficiency. In this article, the genetic and clinical characteristics of these diseases are reviewed in detail.
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PMID:A review of the inherited ataxias: recent advances in genetic, clinical and neuropathologic aspects. 1859 Nov 6

Episodic ataxia (EA) is a rare neurological condition characterized by recurrent spells of truncal ataxia and incoordination. Five genes (KCNA1, CACNA1A, CACNB4, SLC1A3, and UBR4) have been linked to EA. Despite extensive efforts to genetically diagnose EA, many patients remain still undiagnosed. Whole-exome sequencing was carried out in 39 Korean patients with EA to identify pathogenic mutations of the five known EA genes. We also evaluated 40 candidate genes that cause EA as a secondary phenotype or cerebellar ataxia. Eighteen patients (46%) revealed genetic information useful for establishing a molecular diagnosis of EA. In 11 patients, 16 pathogenic mutations were detected in three EA genes. These included nine mutations in CACNA1A, three in SLC1A3, and four in UBR4. Three patients had mutations in two genes, either CACNA1A and SLC1A3 or CACNA1A and UBR4, suggesting that SLC1A3 and UBR4 may act as genetic modifiers with synergic effects on the abnormal presynaptic activity caused by CACNA1A mutations. In seven patients with negative results for screening of EA genes, potential pathogenic mutations were identified in the candidate genes ATP1A2, SCN1A, TTBK2, TGM6, FGF14, and KCND3. This study demonstrates the genetic heterogeneity of Korean EA, and indicates that whole-exome sequencing may be useful for molecular genetic diagnosis of EA.
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PMID:Genetic Variants Associated with Episodic Ataxia in Korea. 2906 94