Publication year
2005Source
Annals of Neurology, 58, 4, (2005), pp. 569-76ISSN
Publication type
Article / Letter to editor
Display more detailsDisplay less details
Organization
Neurology
Human Genetics
Journal title
Annals of Neurology
Volume
vol. 58
Issue
iss. 4
Page start
p. 569
Page end
p. 76
Subject
DCN 2: Functional Neurogenomics; UMCN 3.1: Neuromuscular development and genetic disordersAbstract
Facioscapulohumeral muscular dystrophy (FSHD) progressively affects the facial, shoulder, and upper arm muscles and is associated with contractions of the polymorphic D4Z4 repeat array in 4q35. Recently, we demonstrated that FSHD alleles are hypomethylated at D4Z4. To study potential relationships between D4Z4 hypomethylation and both residual repeat size and clinical severity, we compared the clinical severity score with D4Z4 methylation in unrelated FSHD patients. Correcting the clinical severity score for age at examination improves the parameter to define clinical severity and provides further support for hypomethylation of FSHD alleles. However, a linear relationship between repeat size and clinical severity of the disease cannot be established. Interestingly, FSHD can be separated in two clinical severity classes: patients with residual repeat sizes of 10 to 20 kb are severely affected and show pronounced D4Z4 hypomethylation. In contrast, patients with repeat sizes of 20 to 31kb show large interindividual variation in clinical severity and D4Z4 hypomethylation. Because the majority of familial FSHD cases are represented in this interval and considering the overt variation in clinical severity in these familial cases, it thus is imperative to develop comprehensive allele-specific assays monitoring total D4Z4 methylation to investigate whether interindividual variation in D4Z4 methylation can be translated into a prognostic factor for clinical severity.
This item appears in the following Collection(s)
- Academic publications [238441]
- Faculty of Medical Sciences [90373]
Upload full text
Use your RU credentials (u/z-number and password) to log in with SURFconext to upload a file for processing by the repository team.