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Genetic and Epigenetic Determinants of Low Dysferlin Expression in Monocytes

Lookup NU author(s): Professor Jordi Diaz ManeraORCiD


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Dysferlinopathies are autosomal recessive inherited muscular dystrophies caused by mutations in the gene DYSF. Dysferlin is primarily expressed in skeletal muscle, cardiac muscle, and peripheral blood monocytes. Expression in skeletal muscle and monocytes strongly correlates in healthy and disease states. We evaluated the efficiency of the monocyte assay to detect carriers and to determine the carrier frequency of dysferlinopathies in the general population. We enrolled 149 healthy volunteers and collected peripheral blood samples for protein analysis. While 18 of these individuals with protein levels in the range of 40%-64% were predicted to be carriers by the monocyte assay, subsequent DYSF sequencing analysis in 14 of 18 detected missense variants in only four. Analysis of DNA methylation patterns at the DYSF locus showed no changes in methylation levels at CpG islands and shores between samples. Our results suggest that: (1) dysferlin expression can also be regulated by factors outside of the dysferlin gene, but not related to DNA methylation; (2) carrier frequency and therefore the number of affected individuals could be higher than previously estimated; and (3) although reliable for evaluating dysferlinopathies, the monocyte assay cannot be used to determine the carrier status; for this, a molecular analysis of DYSF must be performed. © 2014 WILEY PERIODICALS, INC.

Publication metadata

Author(s): Gallardo E, Ankala A, Nunez-Alvarez Y, Hegde M, Diaz-Manera J, Luna ND, Pastoret A, Suelves M, Illa I

Publication type: Article

Publication status: Published

Journal: Human Mutation

Year: 2014

Volume: 35

Issue: 8

Pages: 990-997

Print publication date: 01/08/2014

Online publication date: 17/05/2014

Acceptance date: 02/05/2014

ISSN (print): 1059-7794

ISSN (electronic): 1098-1004

Publisher: John Wiley and Sons Inc.


DOI: 10.1002/humu.22591

PubMed id: 24838345


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