UMMS Affiliation

Wellstone Program; Department of Cell and Developmental Biology; King Lab

Publication Date

2013-08-14

Document Type

Article

Disciplines

Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Genetics | Musculoskeletal Diseases | Nervous System Diseases | Neurology | Neuroscience and Neurobiology

Abstract

Facioscapulohumeral muscular dystrophy (FSHD) is a progressive myopathy with a relatively late age of onset (usually in the late teens) compared with Duchenne and many other muscular dystrophies. The current FSHD disease model postulates that contraction of the D4Z4 array at chromosome 4q35 leads to a more open chromatin conformation in that region and allows transcription of the DUX4 gene. DUX4 mRNA is stable only when transcribed from certain haplotypes that contain a polyadenylation signal. DUX4 protein is hypothesized to cause FSHD by mediating cytotoxicity and impairing skeletal muscle differentiation. We recently showed in a cell culture model that DUX4 expression is regulated by telomere length, suggesting that telomere shortening during aging may be partially responsible for the delayed onset and progressive nature of FSHD. We here put our data in the context of other recent findings arguing that progressive telomere shortening may play a critical role in FSHD but is not the whole story and that the current disease model needs additional refinement.

Keywords

facioscapulohumeral muscular dystrophy, FSHD, telomeres, complex genetics, D4Z4 contractions, DUX4, compound heterozygotes, multifactorial

Rights and Permissions

Copyright © 2013 Landes Bioscience. This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.

DOI of Published Version

10.4161/rdis.26142

Source

Stadler G, King OD, Robin JD, Shay JW, Wright WE. Facioscapulohumeral muscular dystrophy: Are telomeres the end of the story? Rare Dis. 2013 Aug 14;1:e26142. doi: 10.4161/rdis.26142. PMID: 25003004; PMCID: PMC3927483. Link to article on publisher's site

Journal/Book/Conference Title

Rare diseases (Austin, Tex.)

Related Resources

Link to Article in PubMed

PubMed ID

25003004

Creative Commons License

Creative Commons Attribution-Noncommercial 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial 3.0 License

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