Genetic aspects of Huntington's disease in Latin America. A systematic review

Abstract

Huntington's disease (HD) is a progressive autosomal dominant illness characterized by involuntary choreic movements, psychiatry and cognitive disturbances. HD is caused by an expansion of CAG repeats in HTT gene. Western countries with major Caucasian ancestry have higher HD prevalence than those found in Asia. Data on HD in Latin America (LA) is sparse. Objective: To present a systematic review on genetic aspects of HD in Latin America. Methods: PubMed and LILACS were searched up to March 2015, reporting confirmed HD cases in LA. Case series, cross-sectional, case-control, and prospective studies were included. Results: From 534 communications, 47 met the eligibility criteria. Population-based studies were not found; minimal prevalence of 0.5-4 / 100,000 was estimated for Venezuela and Mexico. Geographical isolates were well characterized in Venezuela and in Peru. CAG repeats at HTT gene varied between 7-33 and 37-112 in normal and expanded alleles, respectively. Intermediate alleles were found in 4-10% of controls. Ages at onset and the expanded CAG repeats correlated with r from -0.55 to -0.91. While haplotype patterns of Venezuelan and Brazilian chromosomes were similar to those observed in Europeans, haplotypes from Peruvian HD patients did not match the same pattern. Conclusions: The limited number of papers addressing HD in LA suggests that HD is poorly diagnosed in the continent. Minimal prevalence seemed to be halfway between those of Caucasians and Asians. Range of CAG repeats was similar to those of Europeans. Haplotype studies indicate that majority of HD patients might be of Caucasian descent; an Asian origin for some Peruvian patients was proposed.

Action‐semantic and syntactic deficits in subjects at risk for Huntington's disease

“…This would be particularly useful in families for whom genetic, biochemical, or imaging studies are too costly or scantily available, which is often the case in communities characterized by a high prevalence of neurodegenerative disorders. For example, the region targeted in our study (Juan de Acosta, Colombia) is a genetic isolate including high rates of poverty alongside high rates of familial HD (Castilhos et al ., ; De Castro & Restrepo, ). In contexts such as this, the proposed extensions of the present study could promote useful breakthroughs in the quest for sensitive, affordable, and widely available biomarkers of prodromal frontostriatal atrophy.…”

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

“…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, ).…”

The targetable A1 Huntington disease haplotype has distinct Amerindian and European origins in Latin America

“…4,7 HD has been reported in many countries of Latin America, but detailed genetic investigations are lacking. 10 Early clinical descriptions were reported in Cuba and Brazil, and subsequently in Argentina, Mexico, Peru, Chile, and Colombia. 11 No population-based prevalence estimates of HD are available in Latin America, but a major focus of HD in Latin America and the world is in the state of Zulia, surrounding Lake Maracaibo in Venezuela.…”

“…12 Across Latin America, the HD mutation is believed to originate from European founders with subsequent admixture in indigenous populations. 10,12 Limited haplotyping studies of HD in Latin America suggest that the HD mutation occurs on specific haplotypes, although not necessarily from European founders. 10 HTT haplotypes in Venezuelan patients, including the CCG repeat in exon 1 (GRCh37 chr4:g.3076673_3076675 [7]) and Δ2642 codon deletion in exon 58 (GRCh37 chr4: g.3230411_3230413delGAG), 13 suggest a common origin of the HD mutation among affected families of Venezuela, but without definitive data of European ancestry.…”

“…10,12 Limited haplotyping studies of HD in Latin America suggest that the HD mutation occurs on specific haplotypes, although not necessarily from European founders. 10 HTT haplotypes in Venezuelan patients, including the CCG repeat in exon 1 (GRCh37 chr4:g.3076673_3076675 [7]) and Δ2642 codon deletion in exon 58 (GRCh37 chr4: g.3230411_3230413delGAG), 13 suggest a common origin of the HD mutation among affected families of Venezuela, but without definitive data of European ancestry. 14 (HTT exon numbering follows Ensembl transcript HTT-001/ENST00000355072.9, NCBI reference mRNA NM_002111.8, and exon numbering originally described in Ambrose et al 13 )…”