Mutation status of the IT-15 ( HTT ) gene in ecuadorian families with Huntington’s disease

Abstract

Huntington disease (HD) is a progressive neurodegenerative disorder with an autosomal dominant inheritance that affects 1 per 10.000 individuals. It is caused by the IT-15 gene on chromosome 4p16.3 that has, in its first exon, an unstable expansion of (CAG)n trinucleotide which encodes a polyglutamine region in huntingtin; the expansion promotes neurodegeneration. This first descriptive study was focused on evaluating the CAG trinucleotide expansion in Ecuadorian affected individuals and their family members at risk in order to enclose the first approximation of the disease status in Ecuador. Through PCR, nested PCR and automatic sequencing, we have genotyped 42 individuals from nine Ecuadorian families clinically diagnosed with HD. Twenty-eight people tested positive for the mutation with an average CAG number of the expanded allele of 57 ± 7.9 (49-78), seven of which have not thus far presented Chorea. The average repeats of the normal alleles were 24 ± 8.4 (15-28). Two individuals with 32 and 37 repeats showed moderately expanded alleles while a single case was found to be de novo with 53 CAG. An inverse relationship between the number of repeats and age of onset of symptoms was observed. Generational instability was transmitted in 21.4% of the cases with notable instability in paternal inheritance in one case. Genetic diagnosis of the IT-15 gene is extremely important, larger studies in different regions and ethnic groups are needed to better know the behavior of Huntington’s disease in Ecuador.