Progression of somatic CTG repeat length heterogeneity in the blood cells of myotonic dystrophy patients

被引:126
作者
Martorell, L
Monckton, DG
Gamez, J
Johnson, KJ
Gich, I
de Munain, AL
Baiget, M
机构
[1] Hosp Sant Pau, Unitat Genet Mol, Barcelona 08025, Spain
[2] Hosp Sant Pau, Inst Recerca, Barcelona 08025, Spain
[3] Univ Glasgow, Inst Biomed & Life Sci, Div Mol Genet, Glasgow, Lanark, Scotland
[4] Hosp Ntra Sra Aranzazu, Dept Neurol, San Sebastian, Spain
[5] Hosp Gen Valle Hebron, Dept Neurol, Barcelona, Spain
关键词
D O I
10.1093/hmg/7.2.307
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The genetic basis of myotonic dystrophy (DM) is the expansion of an unstable CTG repeat in the 3' UTR of the DM protein kinase gene on chromosome 19, One of the principal features of the DM mutation is an extraordinarily high level of somatic mosaicism, due to an extremely high degree of somatic instability both within and between different tissues, This instability appears to be biased towards further expansion and continuous throughout the life of an individual, features that could be associated with the progressive nature of the disease, Although increasing measured allele size between patients clearly correlates with an increased severity of symptoms and an earlier age of onset, this correlation is not precise and measured allele length cannot be used as an accurate predictor of age of onset, In order to further characterize the dynamics of DM CTG repeat somatic instability, we have studied repeat length changes over time in 111 myotonic dystrophy patients with varying clinical severity and CTG repeat size over time intervals of 1-7 years. We have found a direct progression of the size heterogeneity over time related to initial CTG repeat size and the time interval and always biased towards further expansion, Attempts to mathematically model the dynamics have proved only partially successful suggesting that individual specific genetic and/or environmental factors also play a role in somatic mosaicism.
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收藏
页码:307 / 312
页数:6
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