Type 1 FSHD with 6-10 Repeated Units: Factors Underlying Severity in Index Cases and Disease Penetrance in Their Relatives Attention.

Details

Serval ID
serval:BIB_5C6CF1141692
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Type 1 FSHD with 6-10 Repeated Units: Factors Underlying Severity in Index Cases and Disease Penetrance in Their Relatives Attention.
Journal
International journal of molecular sciences
Author(s)
Salort-Campana E., Fatehi F., Beloribi-Djefaflia S., Roche S., Nguyen K., Bernard R., Cintas P., Solé G., Bouhour F., Ollagnon E., Sacconi S., Echaniz-Laguna A., Kuntzer T., Levy N., Magdinier F., Attarian S.
ISSN
1422-0067 (Electronic)
ISSN-L
1422-0067
Publication state
Published
Issued date
23/03/2020
Peer-reviewed
Oui
Volume
21
Number
6
Pages
2221
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Molecular defects in type 1 facioscapulohumeral muscular dystrophy (FSHD) are caused by a heterozygous contraction of the D4Z4 repeat array from 1 to 10 repeat units (RUs) on 4q35. This study compared (1) the phenotype and severity of FSHD1 between patients carrying 6-8 vs. 9-10 RUs, (2) the amount of methylation in different D4Z4 regions between patients with FSHD1 with different clinical severity scores (CSS). This cross-sectional multicenter study was conducted to measure functional scales and for genetic analysis. Patients were classified into two categories according to RUs: Group 1, 6-8; Group 2, 9-10. Methylation analysis was performed in 27 patients. A total of 99 carriers of a contracted D4Z4 array were examined. No significant correlations between RUs and CSS (r = 0.04, p = 0.73) and any of the clinical outcome scales were observed between the two groups. Hypomethylation was significantly more pronounced in patients with high CSS (>3.5) than those with low CSS (<1.5) (in DR1 and 5P), indicating that the extent of hypomethylation might modulate disease severity. In Group 1, the disease severity is not strongly correlated with the allele size and is mostly correlated with the methylation of D4Z4 regions.
Keywords
Adult, Alleles, Attention, Cross-Sectional Studies, DNA Methylation, Female, Genetic Association Studies, Genetic Predisposition to Disease, Genotype, Humans, Male, Middle Aged, Muscular Dystrophy, Facioscapulohumeral/diagnosis, Muscular Dystrophy, Facioscapulohumeral/genetics, Penetrance, Phenotype, Repetitive Sequences, Nucleic Acid, Severity of Illness Index, FSHD, Facioscapulohumeral muscular dystrophy, association, correlation, genotype, methylation, phenotype
Pubmed
Web of science
Open Access
Yes
Create date
01/04/2020 18:30
Last modification date
23/12/2020 6:24
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