Estimation of the age at onset in spinocerebellar ataxia type 2 Cuban patients by survival analysis
Center for Investigation and Rehabilitation of Hereditary Ataxias (CIRAH), Holguín Province, Cuba. Clinical Genetics
(Impact Factor: 3.93).
08/2010; 78(2):169-74. DOI: 10.1111/j.1399-0004.2009.01358.x
Almaguer-Mederosa LE, Falcón NS, Almira YR, Zaldivar YG, Almarales DC, Góngora EM, Herrera MP, Batallán KE, Armiñán RR, Manresa MV, Cruz GS, Laffita-Mesa J, Cyuz TM, Chang V, Auburger G, Gispert S, Pérez LV. Estimation of the age at onset in spinocerebellar ataxia type 2 Cuban patients by survival analysis.
Previous studies have investigated the close association that exists between CAG repeat number and the age at onset in SCA2 = spinocerebellar ataxia type 2. These studies have focused on affected individuals. To further characterize this association and estimate the risk of a carrier developing SCA2 at a particular age as a function of a specific CAG repeat size, we have analyzed a large group of 924 individuals, including 394 presymptomatic and 530 affected individuals with a CAG repeat length of 32–79 units. Using a Kaplan–Meier survival analysis, we obtained cumulative probability curves for disease manifestation at a particular age for each CAG repeat length in the 34–45 range. These curves were significantly different (p < 0.001) and showed small overlap. All these information may be very valuable in predictive-testing programs, in the planning of studies for the identification of other genetic and environmental factors as modifiers of age at onset, and in the design of clinical trials for people at enlarged risk for SCA2.
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- "Ensembl database (Ensembl release 79 -March 2015) show that this gene has 2221 different validated variants, among all of these variants there is the rs1530440 , which was confirmed by several studies to be associated with hypertension or blood pressure , furthermore it was replicated in several different population (Newton-Cheh et al.,2009; Jennifer et al.,2011; Yang et al.2012) The human ATXN2 gene encode for the ataxin-2 protein which is well known to be the molecular bases of spinocerebellar ataxia-2 (SCA2) disease , (Almaguer-Mederosa et al., 2010). The complete image of Ataxin-2 protein role in the cell still under investigation and several models are proposed to explain the main role of this protein , in general, it is accepted to has a certain role/s in RNA regulation . "
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ABSTRACT: Hypertension is the persisted elevation of blood pressure above the normal rates. About 40% of adults in glob suffered from hypertension which Estimated to cause about 12.8% of total annual deaths. This high mortality can be explained because of its major role in the development of cerebrovascular and coronary heart diseases. All hypertensive cases, that do not have an explained etiology are called essential hypertension (EH), this consists about 95% of the total diagnosed hypertension cases. otherwise, it is called secondary hypertension. The recent studies implicate many genes to have an effect on the development and the susceptibility of essential hypertension. genes variants such as; rs653178 of Ataxin-2 (ATX2N) gene and rs1530440 of chromosome 10 open reading frame 107 (C10orf107) gene, represent the top hit variants that found to be significantly associated with essential hypertension in several populations. We aimed by this project, to conduct a case-control association study to evaluate the association of rs653178 and rs1530440 genetic variants with essential hypertension, in one of Iraqi provinces (Babylon) by enrolling individuals from Arab ancestry. The study enrolled 100 unrelated cases of well diagnosed essential hypertensive patients and a 70 unrelated controls of carefully selected normotensive individuals. For genotyping; we designed and optimized a polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) method with the presence of internal splicing sites. Concerning ATX2N rs653178, there was no significant allelic or genotypic association achieved, both patients and control groups did not deviate from Hardy-Weinberg equilibrium distribution , furthermore , the same results were achieved when the samples segregated into male and females. Concerning C10orf107 rs1530440, there was no significant allelic association achieved, but there was a significant difference in the distribution of TT genotype between patient and control groups (p =0.032) , the T allele represent a protective recessive allele which when present as homozygote (TT) it will confer a resistant to the carrier individual, all TT genotype carriers individual (N= 4) were normotensive. Furthermore, There were no significance association recorded when the samples segregated into males and females, and both patients and control groups did not deviated from Hardy-Weinberg equilibrium distribution in all studied groups. We conclude that C10orf107 genes variants represent a genetic factors which can modulate the essential hypertension susceptibility in Arab population of Babylon province. Abbreviations: Chronic kidney disease genetic Consortium: CKDGen consortium, Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium: CHARGE Consortium, disease susceptibility locus: DSL, Essential hypertension :EH, Global Blood Pressure Genetics Consortium: Global BPgen Consortium, linkage disequilibrium: LD , polymerase chain reaction-restriction fragment length polymorphism: PCR-RFLP, polymerase chain reaction: PCR , quantitative trait loci: QTL , single nucleotide polymorphism: SNP.
Research Journal of Pharmaceutical, Biological and Chemical Sciences 01/2015; 6(6). · 0.35 Impact Factor
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ABSTRACT: Parkinson's disease is a degenerative central nervous system disorder that often impairs motor skills, speech and other functions. We discovered a large Chinese family showing primarily parkinsonism symptoms with autosomal dominant inheritance. Six affected individuals in the family showed typical parkinsonism symptoms, including pill-rolling tremor. Two other affected individuals showed cerebellar ataxia symptoms. A whole-genome scan using the 50K single nucleotide polymorphism array with three different linkage methods detected two positive regions on chromosome 12q24.1 and 5q13.3. The ATXN2 gene, responsible for spinocerebellar ataxia type 2 (SCA2) was located precisely in the center of the positive region on chromosome 12. Further analysis of SCA2 revealed heterozygous pathological CAG expansions in the family. The affected individuals' symptoms were typical of parkinsonism, but complex. Inverse correlation between CAG repeat size and age of onset is not obvious in this pedigree. This parkinsonism-predominant SCA2 family shared the same disease gene locus with other 'standard' SCA2 families, but it is possible that variations in one or more modifier genes might account for the parkinsonism-predominant SCA2 predisposition observed in this pedigree.
Journal of Human Genetics 02/2011; 56(4):330-4. DOI:10.1038/jhg.2011.14 · 2.46 Impact Factor
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ABSTRACT: 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 Purkinje cells in the cerebellum and several pontine, mesencephalic, and thalamic neurons among other cells. Worldwide, SCA2 is the second most frequent type of spinocerebellar ataxia, only surpassed by SCA3. Nevertheless, in Holguin, Cuba, the disease reaches the highest prevalence, resulting from a putative foundational effect. This review discusses the most important advances in the genotypical and phenotypical studies of SCA2, highlighting the comprehensive characterization reached in Cuba through clinical, neuroepidemiological, neurochemical, and neurophysiological evaluation of SCA2 patients and pre-symptomatic subjects, which has allowed the identification of new disease biomarkers and therapeutical opportunities. These findings provide guidelines, from a Cuban viewpoint, for the clinical management of the disease, its diagnosis, genetic counseling, and therapeutical options through rehabilitative therapy and/or pharmacological options.
The Cerebellum 03/2011; 10(2):184-98. DOI:10.1007/s12311-011-0265-2 · 2.72 Impact Factor
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