INTERGENERATIONAL STABILITY OF THE MYOTONIC-DYSTROPHY PROTOMUTATION

The amplification of the CTG trinucleotide repeat in myotonic dystroph y (DM) correlates with increasingly severe phenotypes. We designate it s minimal amplification the 'protomutation' since it is the mutation i tself at an early stage of intergenerational evolution and is associat ed with very mild clinical signs. From the study of 536 DM mutation ca rriers (from 158 affected families), a total of 60 DM-parent/DM-offspr ing pairings were identified in which the parent had the protomutation . We found a strong correlation between the protomutation length and t he amplification observed in the next generation. We also observed the stable transmission of the protomutation through successive generatio ns. This stability may explain the maintenance in the population of th is autosomal dominant disease despite the low reproductive fitness of severe DM phenotypes.