Barceló J M, Mahadevan M S, Tsilfidis C, MacKenzie A E, Korneluk R G
Department of Microbiology and Immunology, University of Ottawa, Ontario, Canada.
Hum Mol Genet. 1993 Jun;2(6):705-9. doi: 10.1093/hmg/2.6.705.
The amplification of the CTG trinucleotide repeat in myotonic dystrophy (DM) correlates with increasingly severe phenotypes. We designate its minimal amplification the 'protomutation' since it is the mutation itself at an early stage of intergenerational evolution and is associated with very mild clinical signs. From the study of 536 DM mutation carriers (from 158 affected families), a total of 60 DM-parent/DM-offspring pairings were identified in which the parent had the protomutation. We found a strong correlation between the protomutation length and the amplification observed in the next generation. We also observed the stable transmission of the protomutation through successive generations. This stability may explain the maintenance in the population of this autosomal dominant disease despite the low reproductive fitness of severe DM phenotypes.
强直性肌营养不良（DM）中CTG三核苷酸重复序列的扩增与越来越严重的表型相关。我们将其最小扩增称为“前突变”，因为它是代际进化早期的突变本身，且与非常轻微的临床症状相关。通过对536名DM突变携带者（来自158个受影响家庭）的研究，共确定了60对DM父母/ DM后代配对，其中父母具有前突变。我们发现前突变长度与下一代中观察到的扩增之间存在强烈相关性。我们还观察到前突变在连续几代中的稳定传递。这种稳定性可能解释了尽管严重DM表型的生殖适应性较低，但这种常染色体显性疾病仍在人群中维持的原因。
