Enfermedades causadas por expansión de tripletes

Abstract

Today we know of a group of mutations caused by the expansion of nucleotide triplets, which are very unstable in meiosis and mitosis. Four types of triplets have the capacity for pathogenic expansion in human beings (CGG/ GCC, CAG/GTC, CTG/GAC and GAA/CTT) and maybe located both in coding sequences (bulbospinal muscular atrophy, Huntington's disease and certain spinocerebellar ataxias) and non-coding sequences (fragile X syndrome, Friedreich's ataxia, myotonic dystrophy). Trinucleotide expansion may lead to gains or losses in gene functioning and seems to be associated to a variety of factors, some of which are directly related with the expansive process (cis-acting) and others whose interaction with the triplets helps to make them increasingly more unstable (trans-acting). Medium-sized expansions (pre-mutations), although clinically silent, do show a marked tendency to expand into complete mutations during the transition along the germinal line. The models that have been proposed to explain triplet expansion involve gene recombination and replication processes; however, they have not fully succeeded in explaining the phenomena related to mutation or phenotypic expression in these diseases.This work examines the most recent concepts related to the dynamic mutation processes that give rise to human diseases; it also reviews the most important clinico-biological aspects observed in those diseases.Dynamic mutation processes represent a new concept in the molecular biology of gene mutations. An ever increasing number of pathologies are caused by this type of DNA alterations, which, as a whole, display very interesting clinico-biological characteristics.