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

Abstract

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.

The molecular epidemiology of Huntington disease is related to intermediate allele frequency and haplotype in the general population

“…Hispanic Americans in our study were found to have the highest IA frequency of all evaluated groups (5.6%). In line with these observations, a recent systematic review of global IA prevalence observed that the highest IA frequency in the general population detected to date (8.7%) was found in Brazilians (Apolinario, Paiva, & Agostinho, ).…”

“…These data suggest that the genetic prevalence rate of HD in admixed populations of Latin America may in fact exceed the prevalence rate in populations of predominant European ancestry. However, only a limited number of studies reporting IA frequencies for Latin America are available (Apolinario et al, ) and recent population‐based prevalence estimates of HD for most of the region are unavailable (Castilhos et al, ; Paradisi, Hernandez, & Arias, ; Rawlins et al, ). The term Hispanic broadly refers to persons of Latin American or Spanish descent, representing a heterogonous group of individuals with varying degrees of admixture from European, African, and Native American ancestry (Bedoya et al, ; Gravel et al, ).…”

Evaluation of language functions in Huntington's disease

“…Huntington hastalığı (HH) otozomal dominant geçişli korenin en sık sebebi olan nörodejeneratif bir hastalıktır [1]. HH'nin kesin tanısı, 4.…”

“…Burada en sık görülen bozukluk depresyondur. Kognitif bozukluk ise özellikle yürütücü fonksiyonlarla ilişkilidir ve seyir sonunda demansa dönüşür [1].…”

Huntington Hastalığında Dikkat Fonksiyonlarının Değerlendirilmesi

“…Huntington hastalığı (HH) otozomal dominant geçişli nörodejeneratif bir hastalıktır 1 .HH ile ilgili genom (IT-15)kromozom 4'ün kısa bacağında (4p16.3 )bulunmaktadır. IT-15 geni huntington proteinini kodlamaktadır.…”