Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Episodic ataxia type 2 is an autosomal dominant disorder with attacks of vertigo and ataxia which respond to acetazolamide treatment. The gene, distinct from the KCNA1 responsible for episodic ataxia type 1, has been mapped on chromosome 19p13 in a 11-12 cM region. A large Italian kindred affected with acetazolamide-responsive episodic ataxia is reported, with onset in adulthood, a strong vestibular component during attacks and a high frequency of cerebellar vermis degeneration. The genetic analysis (i) showed strong linkage between the disease and the 19p13 microsatellite markers in a region which widely overlaps that previously reported and (ii) set a new distal boundary of the gene-containing region. Combining present and previous mapping data, the gene of episodic etaxia type 2 is most probably located in an interval approximately 1.5 Mb between markers D19S221 and D19S226.
 ...
PMID:Acetazolamide-responsive episodic ataxia in an Italian family refines gene mapping on chromosome 19p13. 918 51

The hereditary ataxias comprise a complex group of neurological disorders involving the cerebellum and its connections. Several classifications based on clinical and/or pathological data have been only partially successful. Recent progress in molecular genetics has identified the genic loci of hereditary ataxias and has allowed a more precise diagnosis of distinct genetic diseases. Trinucleotide repeat expansions has been recognized as a mechanism of disease in some autosomal dominant spinocerebellar ataxias (ADCA) (SCA1 to SCA7), including Machado-Joseph disease/SCA3, probably the most common form of ADCA in South Brazil, and Friedreich ataxia (GAA expansion-chromosome 9p). Familial alpha-tocopherol deficiency (chromosome 8q) may have a Friedreich ataxia phenotype and responds to the oral supplementation with vitamin E. Familial episodic ataxias with (EA1-chromosome 12p) and without (chromosome 19p-EA2) myokimia were identified, the first one caused by point mutations in the gene encoding the KCNA1 potassium voltage-gated channel. The gene responsible for ataxia-teleangiectasia (chromosome 11q) was found to encode a putative DNA binding protein kinase (ATM), related to the cell cycle control. One to 3% of the population are heterozygotic ATM gen carry and pose a higher risk of cancer when exposed to ionizing radiation. Molecular biology has provided us with useful tools to diagnosis and genetic counseling and, hopefully, will provide us with a better understanding of the pathogenesis and eventual treatment of the several forms of hereditary ataxias.
 ...
PMID:[Hereditary cerebellar ataxias: from hammer to genetics]. 962 25

Familial episodic ataxias are unusual hereditary disorders of early onset characterized by recurrent episodes of ataxia. Most patients recover fully between attacks, but some may develop progressive ataxia with cerebellar atrophy. There are two subtypes of episodic ataxia: type 1 (EA1), with interictal myokymia, and type 2 (EA2), with interictal nystagmus. Stress and fatigue can trigger ataxic spells, which can be responsive to acetazolamide. These clinical features are reminiscent of other channelopathies or paroxysmal neurologic disorders with progressive features caused by ion channel mutations. Familial episodic ataxias indeed are channelopathies. EA1 is caused by mutations in a potassium channel-encoding gene, whereas EA2 is caused by mutations in a calcium channel-encoding gene, which is also the disease-causing gene in spinocerebellar ataxia type 6 and several kindreds with familial hemiplegic migraine. Treatment with acetazolamide can be effective in decreasing the frequency of attacks and is generally well tolerated. Understanding the mechanism of action of acetazolamide and the functional consequences of these mutations will help one to develop a rational pharmacologic treatment for these disorders, which may share similar mechanisms with benign recurrent vertigo and more common forms of migraine.
 ...
PMID:Familial Episodic Ataxias and Related Ion Channel Disorders. 1109 68

The past few years have seen the elucidation of several neurological diseases caused by inherited mutations of ion channels. In contrast to many other types of genetic disorders, the "channelopathies" can be studied with high precision by applying electrophysiological methods. This review evaluates the success of this approach in explaining the mechanisms of two forms of episodic ataxia that are known to be caused by mutations of ion channels: episodic ataxia type 1 (EA1, caused by K+ channel mutations) and episodic ataxia type 2 (EA2, caused by Ca2+ channel mutations). Although both of these disorders are rare, they raise many important questions about the roles of identified channels in brain function. Indeed, a resolution of the mechanisms by which both diseases occur will represent a major milestone in understanding diseases of the CNS, in addition to opening the way to novel possible treatments.
 ...
PMID:The inherited episodic ataxias: how well do we understand the disease mechanisms? 1148 47

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 ataxia type 2 is a prototypical episodic vertigo and ataxia syndrome that is caused by mutations in the calcium channel gene CACNA1A. Recent discoveries regarding the molecular mechanisms that underlie this syndrome provide a model for understanding the more common familial episodic vertigo syndromes, particularly those associated with migraine. Vertigo due to cerebrovascular disease can be of peripheral or central origin, and can mimic more benign peripheral vestibular disorders. Small infarcts in the cerebellum and lateral medulla can present with vertigo without other localizing symptoms.
 ...
PMID:Episodic vertigo: central nervous system causes. 1179 46

In the past decade, the genetic etiologies accounting for most cases of adult-onset dominant cerebellar ataxia have been discovered. This group of disorders, generally referred to as the spinocerebellar ataxias (SCAs), can now be classified by a simple genetic nosology, essentially a sequential list in which each new SCA is given a number. However, recent advances in the elucidation of SCA pathogenesis provide the opportunity to subclassify the disorders into three discrete groups based on pathogenesis: 1) the polyglutamine disorders, SCAs 1, 2, 3, 7, and 17, which result from proteins with toxic stretches of polyglutamine; 2) the channelopathies, SCA6 and episodic ataxia types 1 and 2 (EA1 and EA2), which result from disruption of calcium or potassium channel function; and 3) the gene expression disorders, SCAs 8, 10, and 12, which result from repeat expansions outside of coding regions that may quantitatively alter gene expression. SCAs 4, 5, 9, 11, 13-16, 19, 21, and 22 are of unknown etiology, and may or may not fit into one of these three groups. At present, most diagnostic and therapeutic strategies apply equally to all of the SCAs. Therapy specific for individual diseases or types of diseases is a realistic goal in the foreseeable future.
 ...
PMID:The spinocerebellar ataxias: order emerges from chaos. 1216 26

Episodic ataxia type 2 (EA2) has been reported to result from mutations in the CACNA1A gene, located on chromosome 19p13. We describe a family with episodic ataxia, clinically indistinguishable from EA2, that was not caused by CACNA1A gene mutation. The proband is an 11-year-old boy, who has had 6 cerebellar ataxic attacks since 8 years of age. His attacks occurred almost monthly, lasting for 2 to 3 days. He was treated successfully with acetazolamide. His identical twin, mother and grandmother developed ataxic attacks at age 10, 34, and 50, respectively. The symptoms in his grandmother improved gradually without medication. His mother and identical twin took acetazolamide with a good response. We examined the CACNA1A gene for this family but did not detect any mutations. Furthermore, there was no evidence of genetic linkage between the CACNA1A gene and the symptomatic patients in this family. This suggests that the cause of EA2 can be heterogeneous, that is, defects of genes other than CACNA1A might be the cause of EA2.
 ...
PMID:A family of episodic ataxia type 2: no evidence of genetic linkage to the CACNA1A gene. 1252 75

Episodic ataxia type 2 (EA-2) is an autosomal dominant neurological disorder, characterized by episodes of ataxia, vertigo, nausea, nystagmus, and fatigue, associated with acetazolamide responsiveness. The disease is caused by mutations in the P/Q-type calcium channel Ca(v)2.1 subunit gene, CACNA1A, located on chromosome 19p13.2. We analyzed a family with 13 affected individuals for linkage to this locus and reached a two-point maximum LOD score of 4.48. A novel CACNA1A mutation, IVS36-2A>G, at the 3' acceptor splice site of intron 36 was identified by sequencing. It is the first described CACNA1A acceptor splice site mutation and the most C-terminal EA-2-causing mutation reported to date.
 ...
PMID:Novel splice site CACNA1A mutation causing episodic ataxia type 2. 1453 Sep 26

Episodic ataxia type 2 (EA2) is a dominantly inherited disorder, characterized by spells of ataxia, dysarthria, vertigo, and migraines, associated with mutations in the neuronal calcium-channel gene CACNA1A. Ataxic spells lasting minutes to hours are provoked by stress, exercise, or alcohol. Some patients exhibit nystagmus between spells and some develop progressive ataxia later in life. At least 21 distinct CACNA1A mutations have been identified in EA2. The clinical and genetic complexities of EA2 have offered few insights into the underlying pathogenic mechanisms for this disorder. We identified a novel EA2 kindred in which members had ataxic spells induced by fevers or high environmental temperature. We identified a novel CACNA1A mutation (nucleotides 1253+1 G-->A) that was present in all subjects with febrile spells or ataxia. Moreover, we found that, regardless of age or interictal clinical status, all affected subjects had objective evidence of abnormal saccades, ocular fixation, and postural stability. These findings suggest that early cerebellar dysfunction in EA2 results from the intrinsically abnormal properties of the CACNA1A channel rather than a degenerative process.
 ...
PMID:Novel CACNA1A mutation causes febrile episodic ataxia with interictal cerebellar deficits. 1468 82


1 2 3 4 Next >>