[A new mechanism of mutation in man: expansion of trinucleotide repeats].
An analysis of a novel, recently discovered class of mutations in man - an expansion, i.e., an increase of the copy number of intragenic unstable trinucleotide repeats - is presented. The expansion of trinucleotide repeats causes the development of at least seven hereditary diseases which damage the nervous system: the fragile X chromosome syndrome (two separate variants of the disease - FRAXA and FRAXE), myotonic dystrophy, spinal and bulbar Kennedy's amyotrophy, Huntington's chorea, type 1 spinocerebellar ataxia, and dentatorubral-pallidolyusian atrophy. The discovery of triplet expansion allows a satisfactory explanation on the molecular level of a series of unusual clinical genetic phenomena, such as anticipation, the ¿paternal transmission¿ effect, the ¿Sherman paradox¿, and others. The common properties and the distinctions of unstable trinucleotide mutations in the above-mentioned nosologic forms are analyzed comprehensively among for the mechanism by which these mutations cause disease, the time of their appearance in ontogenesis, and various clinical genetic correlations. The evolutionary origin of this class of mutations and, in particular, the role of alleles with an ¿intermediate¿ triplet number, which are the persistent reservoir of mutations arising de novo in a population, are also discussed. The possible implication of unstable trinucleotide repeats for a series of other hereditary diseases, such as spinocerebellar ataxia of type 2, Machado-Joseph disease, hereditary spastic paraplegia, essential tremor, schizophrenia and others, is also suggested.
Illarioshkin
S N
SN
Ivanova-Smolenskaia
I A
IA
Markova
E D
ED
D030342:Genetic Diseases, Inborn / Q000235:genetics; D006801:Humans; D009154:Mutation; D018911:Trinucleotide Repeats
Novyĭ mekhanizm mutatsii u cheloveka: ékspansiia trinukleotidnykh povtorov.