Uncovering the Genetic and Molecular Features of Huntington's Disease in Northern Colombia

Abstract

Abstract Background The second world's most extensive cluster of patients affected with Huntington’s disease (HD), a genetic disorder caused by a CAG trinucleotide expansion in the huntingtin (HTT) gene, inhabits Juan de Acosta, a city located on the Caribbean coast of Colombia. This group represents the second most extensive pedigree clustering HD in the world. Methods We included 291 descendants of families living in Juan de Acosta, Colombia, who had at least one member with HD. Blood samples were obtained, and genomic DNA was extracted. The HTT CAG expansion was quantified using an amplicon sequencing protocol. Statistical and bioinformatic analyses were conducted using several modules implemented in R. Statistical threshold significance was set at P < 0.05. Results A total of 33 HD patients were analyzed, and a mean of 21.91 HTT CAG repeats with a standard deviation of 8.92 copies was obtained. The most affected individuals were adults, and the most common primary and secondary alleles were 17/7 and 17/10, respectively. Mosaicism increased with age in participants with HD, and slippage analyses revealed differences by HD allele type for the secondary allele, but no significant differences were observed by sex. Slippage tended to increase with the number of CAG repeats in participants with HD, but the increase was not statistically significant. The most common haplotype was 17/7_17/10. Conclusion This study analyzed the genetic and molecular features of HD by examining 291 participants, including 33 with HD. Mosaicism was found to increase with age in subjects with HD, particularly for the secondary allele; the most common haplotype was 17/7_17/10. Slippage for the secondary allele varied by HD allele type, but no significant difference in slippage was observed by sex. The findings offer valuable insights into the disease and could have implications for future research and clinical management.