Implicaciones clínicas y genéticas de las mutaciones dinámicas en clínica neuropediátrica

Abstract

Dynamic mutations are a new type of genetic alteration identified in recent years. They are due to an increased number of repetitions of a particular trinucleotide and are associated with a particular group of neurological and/or neuromuscular disorders. They are characterized by intergenerational and intragenerational instability. There is an inversely proportional relationship between the number of repetitions and the age at which the first symptoms are seen (genetic anticipation). To date 13 disorders, due to this type of mutation, have been described. Some, such as sex-linked mental retardation (fragile X), myotonic dystrophy or Friedreich's ataxia involve an anomalous number of repetitions, reaching over a thousand of a given trinucleotide. Another group known as the polyglutamine disorders, since the CAG trinucleotide is repeated in all cases (dominant and familial ataxias, Huntington's disease) have an increased number of repetitions but there are less than a hundred of them. Finally, recently a third group has been described, oculo-pharyngeal dystrophy with less than a dozen repetitions. Why an increased number of repetitions of a trinucleotide found in or out of a gene is associated with a particular disorder is one of the questions raised by these mutations and which is starting to be discovered.