Ataxia espinocerebelosa tipo 2 (parte A): epidemiología y características clínicas y genéticas

Published on Jan 1, 2014
Luis Velázquez-Pérez24
Estimated H-index: 24
,
Oscar Hernández-Hernández12
Estimated H-index: 12
+ 3 AuthorsJonathan J. Magaña15
Estimated H-index: 15
Source
Abstract
La ataxia espinocerebelosa tipo 2 (SCA2) es una enfermedad genetica con un patron de herencia autosomico dominante que se caracteriza por atrofia cerebelosa asociada con movimientos sacadicos lentos, hiporreflexia temprana, temblor postural severo, neuropatia periferica, desordenes cognitivos y otras caracteristicas multisistemicas. La SCA2, una de las ataxias mas comunes a nivel mundial, es causada por la expansion anormal de un triplete repetido CAG presente en el gen ATXN2. Los pacientes con SCA2 presentan mas de 32 y hasta cientos de repetidos CAG. En esta revision se ofrece una descripcion detallada de las principales caracteristicas epidemiologicas, clinicas y geneticas de la SCA2. Asimismo se detalla la experiencia de la aplicacion de programas de diagnostico predictivo en la poblacion cubana, en donde la caracterizacion de las manifestaciones clinicas de la SCA2, en conjunto con el diagnostico molecular oportuno, han permitido establecer esquemas de rehabilitacion para estos pacientes
References49
Newest
Summary Background The effects of ATXN2 expansion on the nervous system arise before the cerebellar syndrome can be diagnosed; however, progression of the underlying early clinical manifestations is unknown. We aimed to assess progression of the main clinical features in early stages of the spinocerebellar ataxia type 2 (SCA2). Methods We did this longitudinal study between Aug 12, 1986, and Sept 3, 2013, in carriers and non-carriers of the SCA2 mutation. We enrolled participants aged 6–60 years...
60 CitationsSource
#1Jonathan J. MagañaH-Index: 15
#2Y. S. Tapia-Guerrero (IPN: Instituto Politécnico Nacional)H-Index: 5
Last. Bulmaro Cisneros (CINVESTAV)H-Index: 23
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Magana JJ, Tapia-Guerrero YS, Vel˜ azquez-P´ ´erez L, Cerecedo-Zapata CM,Maldonado-Rodriguez M, Jano-Ito JS, Leyva-Garcia N, Gonz´alez-Pi na R,˜Martinez-Cruz E, Hern´andez-Hern andez O, Cisneros B. Analysis of CAG´repeats in five SCA loci in Mexican population: epidemiological evidenceof a SCA7 founder effect.Clin Genet 2013. © John Wiley & Sons A/S. Published by BlackwellPublishing Ltd, 2013Spinocerebellar ataxias (SCA) are a heterogeneous group ofneurodegenerative disorders. CAG (cytosine-adeni...
25 CitationsSource
#1Tania Cruz-MariñoH-Index: 7
Last. Milena Paneque (University of Porto)H-Index: 13
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Having reported the world's highest prevalence of spinocerebellar ataxia type 2 (SCA2), health professionals in Cuba developed a program for the predictive testing of this condition. Between February 2001 and December 2011, a total of 1050 individuals requested their inclusion in the presymptomatic testing (PST) program. Their medical records were retrospectively analyzed in the present descriptive study. A total of 768 participants completed the protocol, 204 withdrew and 78 were excluded. The ...
18 CitationsSource
#1Jonathan J. MagañaH-Index: 15
Last. Bulmaro Cisneros (CINVESTAV)H-Index: 23
view all 3 authors...
Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant genetic disease characterized by cerebellar dysfunction associated with slow saccades, early hyporeflexia, severe tremor of postural or action type, peripheral neuropathy, cognitive disorders, and other multisystemic features. SCA2, one of the most common ataxias worldwide, is caused by the expansion of a CAG triplet repeat located in the N-terminal coding region of the ATXN2 gene, which results in the incorporation of a segment of po...
72 CitationsSource
#1Antoni Matilla-Dueñas (Autonomous University of Barcelona)H-Index: 12
#2Marc Corral-Juan (Autonomous University of Barcelona)H-Index: 8
Last. Ivelisse Sánchez (Autonomous University of Barcelona)H-Index: 5
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Spinocerebellar ataxias (SCAs) are a highly heterogeneous group of inherited neurological disorders, based on clinical characterization alone with variable degrees of cerebellar ataxia often accompanied by additional cerebellar and noncerebellar symptoms which in most cases defy differentiation. Molecular causative deficits in at least 31 genes underlie the clinical symptoms in the SCAs by triggering cerebellar and, very frequently, brain stem dysfunction. The identification of the causative mol...
51 CitationsSource
The role of short, large or intermediate normal alleles (ANs) of the ataxin-2 gene in generating expanded alleles (EAs) causing spinocerebellar ataxia type 2 (SCA2) is poorly understood. It has been postulated that SCA2 prevalence is related to the frequency of large ANs. SCA2 shows the highest worldwide prevalence in Cuban population, which is therefore a unique source for studying the relationship between the frequency of large and intermediate alleles and the frequency of SCA2 mutation. Throu...
38 CitationsSource
Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant cerebellar ataxia characterized by a progressive cerebellar syndrome associated to saccadic slowing, peripheral neuropathy, cognitive disorders, and other multisystem features. SCA2 is caused by the abnormal expansion of cytosine–adenine–guanine triplet repeats in the encoding region of the ATXN2 gene and therefore the expression of toxic polyglutamine expansions in the ataxin 2 protein, which cause progressive neuronal death of Purki...
65 CitationsSource
Rapid eye movement (REM) sleep disorders are commonly associated to patients with spinocerebellar ataxia type 2 (SCA2); however, these abnormalities have not been studied in presymptomatic gene carriers. To determine whether the REM sleep pathology is detectable before clinical manifestation of SCA2 and evaluate it as a preclinical biomarker, we studied 36 presymptomatic SCA2 individuals and 36 controls by video-polysomnography (VPSG) and sleep questionnaires. Presymptomatic subjects showed sign...
34 CitationsSource
Nerve conduction is profoundly affected in Spinocerebellar ataxia 2 (SCA2) even before the onset of the disease, but there is no information regarding its progression to the final stage of SCA2. In order to study the progression patterns of nerve conduction abnormalities in SCA2 we performed a prospective follow up evaluation of sensory and motor conduction in 21 SCA2 mutation carriers-initially presymptomatics- and 19 non-SCA2 mutation carriers during 20 years. The earliest electrophysiological...
43 CitationsSource
Abstract The objective of this study was to determine the prevalence of hereditary ataxias in Cuba, with a special focus on the clinical and molecular features of SCA2. Clinical assessments were performed by neurological examinations and application of the SARA scale. Molecular analyses of genes SCA1–3, SCA6, SCA17 and DRPLA identified 753 patients with SCA and 7173 asymptomatic relatives, belonging to 200 unrelated families. 86.79% of all SCA patients were affected with SCA2. In the Holguin pro...
92 CitationsSource
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view all 13 authors...
In Mexico, around six million people have some kind of disability, of which neuromuscular diseases remain one of the most common causes of inability and death. Neuromuscular disorders are rare conditions that affect the muscles, the neuromuscular junction, the peripheral motor nerves and the motor neurons. Their clinical and genetic variability impact in an effective diagnosis; therefore, many cases are identified belatedly or not diagnosed at all, due to lack economic resources or the absence o...
view all 13 authors...
In Mexico, around six million people have some kind of disability, of which neuromuscular diseases remain one of the most common causes of inability and death. Neuromuscular disorders are rare conditions that affect the muscles, the neuromuscular junction, the peripheral motor nerves and the motor neurons. Their clinical and genetic variability impact in an ef fective diagnosis; therefore, many cases are identified belatedly or not diagnosed at all, due to lack economic resources or the absence ...