Huntington disease mutation in Venezuela: age of onset, haplotype analyses and geographic aggregation

Paradisi, Irene; Hernández, Alba; Arias, Sergio

doi:10.1007/s10038-007-0227-1

Cited by 46 publications

(34 citation statements)

References 27 publications

(27 reference statements)

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“…The alleles with higher frequencies were those showing 17 (21.3%), 18 (16.3%), and 19 (15.0%) CAG repeats. On the other hand, the size of expanded alleles ranged from 35 to 112 CAG repeats: the alleles with 41 (14.4%), 42 (10.1%), and 43 (10.1%) CAG repeats were the most frequent ones (Paradisi et al, 2008). As mentioned earlier in this paper, Nance et al (1999) showed a CAG expansion of approximately 250 repeats in a patient with juvenile HD.…”

Section: Resultssupporting

confidence: 66%

“…Considering the genetic profile of HTT polymorphic CAG alleles, the shortest normal allele found in the general population, cited in this review, had seven CAG repeats and was found in Brazil (Raskin et al, 2000), on the other hand, the longest expanded allele had 122 CAG repeats and was found in Venezuela (Paradisi et al, 2008). It is important to mention that Nance et al (1999) showed a CAG trinucleotide repeat expansion of approximately 250 repeats in a patient with juvenile HD -the largest CAG expansion reported within the huntingtin gene; however, our search took into consideration only articles from 2000 to 2015 (Nance et al, 1999).…”

Section: Resultsmentioning

confidence: 86%

“…According to Paradisi et al (2008), in the general population of Venezuela, the estimated frequency of IA carriers was less than 0.05% in 279 individuals with family history of HD. In this study, the allele size in control subjects ranged from 11 to 31 CAG repeats.…”

Section: Resultsmentioning

confidence: 99%

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REVIEW-ARTICLE Intermediate alleles of Huntington’s disease HTT gene in different populations worldwide: a systematic review

2017

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ABSTRACT. Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative disorder caused by a dynamic mutation due to the expansion of CAG repeats in the HTT gene (4p16.3). The considered normal alleles have less than 27 CAG repeats. Intermediate alleles (IAs) show 27 to 35 CAG repeats and expanded alleles have more than 35 repeats. The IAs apparently have shown a normal phenotype. However, there are some reported associations between individuals that bear an IA and clinical HD signs, such as behavioral disturbs. The association of IAs with the presence of clinical signs gives clinical relevance to these patients. We emphasized the importance of determining the frequency of IA alleles in the general population as well as in HD families. Therefore, the aim of this study was to conduct a systematic review, in order to investigate the frequency of IAs in the overall chromosomes of different ethnic groups and of families with HD history worldwide as well as the frequency of individuals who bear the intermediate alleles. We searched indexed articles from the following electronic databases: U.S. National Library of Medicine and the National Institutes of Health (PubMed), Pubmed Central (PMC) and Virtual Health Library (VHL). Therefore, 488 articles were obtained and, of these, 33 had been published in more than one database. We accepted the article of only one database and ended up with 455 articles for this review. The frequency of IAs within the chromosomes of the general population ranged from 0.45 to 8.7% and of individuals with family history of HD ranged from 0.05 to 5.1%. The higher frequency of IAs in the general population (8.7%) was found in one Brazilian cohort.

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Section: Resultssupporting

confidence: 66%

Section: Resultsmentioning

confidence: 86%

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REVIEW-ARTICLE Intermediate alleles of Huntington’s disease HTT gene in different populations worldwide: a systematic review

2017

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“…In Latin America, HD prevalence shows a wide range: 4/100.000 in Mexico City [3] and 1/200.000 in Venezuela [4]. Studies on the estimated genetic admixture in Uruguay showed evidence that the main genetic contribution comes from Europe (84.1%) with a smaller Amerindian (10.4%) and…”

Section: Introductionmentioning

confidence: 96%

Molecular characterization of genes modifying the age at onset in Huntington's disease in Uruguayan patients

Vital¹,

Bidegain²,

Raggio

et al. 2015

International Journal of Neuroscience

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Huntington's disease (HD) is a hereditary neurodegenerative disorder. The genetic cause is an expansion of CAG repeats located in the IT15 gene. Though the number of CAG repeats ((CAG)n) can largely explain the age at onset (AAO) of symptoms, a percentage of its variation could be attributed to modifier genes and to environmental factors. The study aimed to evaluate the influence of genetic modifiers of the AAO of HD including: (CAG)n and del2642 in the IT15 gene, ADORA2A rs5751876, HAP1 rs4523977, PGC1-α rs7665116 and UCH-L1 rs5030732. Eighteen patients with positive family history and HD-suggestive symptoms were recruited. The (CAG)n and gene polymorphisms were determined by different molecular biology techniques. We observed that the (CAG)n influenced in a 64.5% of the variability in the AAO. We also showed that the rs5751876 variant significantly affected this variability. However, the influence of UCH-L1, del2642, HAP1 and PGC1-α gene polymorphisms could not be replicated, perhaps due to small sample size. Genetic studies including the molecular determination of (CAG)n, in addition to other genetic modifiers involved in the variability of the AAO, were first performed in Uruguay. We could replicate in our cohort the anticipation effect on the AAO by the ADORA2A rs5751876. Our results confirm the usefulness of an expanded molecular characterization in HD patients.

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“…Despite being found in populations throughout the world, estimates of HD prevalence suggest a more than 10-fold difference between regions [11], with clusters in Venezuela, Brazil [12,13], and Tasmania [14]. In Israel, the prevalence of HD has not yet been estimated.…”

Section: Introductionmentioning

confidence: 99%

Two Ethnic Clusters with Huntington Disease in Israel: The Case of Mountain Jews and Karaites

et al. 2017

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Background: Worldwide prevalence estimates of Huntington disease (HD) vary widely, with no reliable information regarding the Jewish population in Israel. Methods: This specialized tertiary single-center cross-sectional study assessed clinical, cognitive, and demographic characteristics of 84 HD patients who were treated at the Movement Disorder Unit of the Tel Aviv Medical Center, Israel. Results: Our cohort was composed of one-third Ashkenazi Jews, 27% Mountain Jews (Caucasus Jews), 18% Sephardi Jews, and 21% Karaites, with both Mountain Jews and Karaites over-represented compared to their relevant proportion in the population of the state of Israel, which is less than 1%. No between-group differences were detected regarding the number of CAG (cytosine-adenine-guanine) repeats, age at onset, disease duration, years from symptom onset to diagnosis, gender, years of education, Unified Huntington Disease Rating Scale scores, or the Montreal Cognitive Assessment scores. Conclusion: We detected clustering of HD among the population treated at our Medical Center, which has the only specialized HD clinic in the country, with a high percentage of HD among 2 relatively small subpopulations of Jews: Mountain Jews and Karaites.

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Huntington disease mutation in Venezuela: age of onset, haplotype analyses and geographic aggregation

Cited by 46 publications

References 27 publications

REVIEW-ARTICLE Intermediate alleles of Huntington’s disease HTT gene in different populations worldwide: a systematic review

REVIEW-ARTICLE Intermediate alleles of Huntington’s disease HTT gene in different populations worldwide: a systematic review

Molecular characterization of genes modifying the age at onset in Huntington's disease in Uruguayan patients

Two Ethnic Clusters with Huntington Disease in Israel: The Case of Mountain Jews and Karaites

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