作者
Sarah A Cumming, Cecilia Jimenez-Moreno, Kees Okkersen, Stephan Wenninger, Ferroudja Daidj, Fiona Hogarth, Roberta Littleford, Gráinne Gorman, Guillaume Bassez, Benedikt Schoser, Hanns Lochmüller, Baziel GM van Engelen, Darren G Monckton, OPTIMISTIC Consortium
发表日期
2019/9/3
期刊
Neurology
卷号
93
期号
10
页码范围
e995-e1009
出版商
Lippincott Williams & Wilkins
简介
Objective
To evaluate the role of genetic variation at the DMPK locus on symptomatic diversity in 250 adult, ambulant patients with myotonic dystrophy type 1 (DM1) recruited to the Observational Prolonged Trial in Myotonic Dystrophy Type 1 to Improve Quality of Life—Standards, a Target Identification Collaboration (OPTIMISTIC) clinical trial.
Methods
We used small pool PCR to correct age at sampling biases and estimate the progenitor allele CTG repeat length and somatic mutational dynamics, and AciI digests and repeat primed PCR to test for the presence of variant repeats.
Results
We confirmed disease severity is driven by progenitor allele length, is further modified by age, and, in some cases, sex, and that patients in whom the CTG repeat expands more rapidly in the soma develop symptoms earlier than predicted. We revealed a key role for variant repeats in reducing disease severity and quantified their role in …
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SA Cumming, C Jimenez-Moreno, K Okkersen… - Neurology, 2019