title: REVIEW-ARTICLE Intermediate alleles of Huntington's disease HTT gene in different populations worldwide: a systematic review.
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.
authors.affiliation: Programa de Pós-Graduação em Neurologia, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brasil.
authors.forename: T A
authors.initials: TA
authors.lastname: Apolinário
authors.affiliation: Programa de Pós-Graduação em Neurologia, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brasil.|Programa de Pós-Graduação em Biologia Molecular e Celular, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brasil.|Departamento de Genética e Biologia Molecular, Instituto Biomédico, Rio de Janeiro, RJ, Brasil.
authors.forename: C L A
authors.initials: CL
authors.lastname: Paiva
authors.affiliation: Programa de Pós-Graduação em Neurologia, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brasil polucita@yahoo.com.br.|Centro Universitário FAMINAS, UNIFAMINAS, Muriaé, MG, Brasil polucita@yahoo.com.br.|Fundação Cristiano Varella, Hospital de Câncer de Muriaé, Muriaé, MG, Brasil polucita@yahoo.com.br.|polucita@yahoo.com.br.
authors.forename: L A
authors.initials: LA
authors.lastname: Agostinho
mesh_terms: D000483:Alleles; D001938:Brazil; D005787:Gene Frequency; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D000071058:Huntingtin Protein / Q000235:genetics* / Q000378:metabolism; D006816:Huntington Disease / Q000453:epidemiology / Q000235:genetics*; D009154:Mutation; D019680:Trinucleotide Repeat Expansion
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein