Abstract

CORE A FSHD BIORESOURCES CORE No pathogenic gene(s) have been identified in FSHD and the molecular and cellular pathophysiology remains unclear. Moreover, the complex genetic and epigenetic changes have precluded the development of a representative animal model. Consequently, access to large numbers of well-characterized, patient-derived biological samples remains vital in advancing FSHD research. The overall aim of the proposed FSHD Bioresources Core is to generate wellcharacterized biological resources, collected in a standardized way and that will assist the Program Project's four proposed scientific studies achieve their proposed aims. To this end we will generate sets of biological resources from a) FSHDl subjects, b) FSHD2 (phenotypic) subjects and c) normal control subjects. Each set will include a flash-frozen muscle sample, a myoblast cell line and a skin-derived fibroblast cell line. Each subject will be comprehensively genotyped for the FSHD region and clinically characterized for overall disease severity, strength of the muscle group from which the sample is derived as well as pathologic grading of an adjacent muscle biopsy sample.

Public Health Relevance

This core will enhance the capability of a nascent FSHD biorepository in Rochester and will allow the collection of enough biological resources to serve not only the needs of the proposed Program Project but the needs of the wider FSHD research community as well.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
5P01NS069539-04
Application #
8434930
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Project Start
Project End
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
4
Fiscal Year
2013
Total Cost
$115,100
Indirect Cost

  Institution

Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
078200995
City
Seattle
State
WA
Country
United States
Zip Code
98109

  Publications

Lemmers, Richard J L F; van der Vliet, Patrick J; Vreijling, Jeroen P et al. (2018) Cis D4Z4 repeat duplications associated with facioscapulohumeral muscular dystrophy type 2. Hum Mol Genet 27:3488-3497
Lim, Jong-Won; Wong, Chao-Jen; Yao, Zizhen et al. (2018) Small noncoding RNAs in FSHD2 muscle cells reveal both DUX4- and SMCHD1-specific signatures. Hum Mol Genet :
Lemmers, Richard Jlf; van der Vliet, Patrick J; Balog, Judit et al. (2018) Deep characterization of a common D4Z4 variant identifies biallelic DUX4 expression as a modifier for disease penetrance in FSHD2. Eur J Hum Genet 26:94-106
Balog, Judit; Goossens, Remko; Lemmers, Richard J L F et al. (2018) Monosomy 18p is a risk factor for facioscapulohumeral dystrophy. J Med Genet 55:469-478
Campbell, Amy E; Shadle, Sean C; Jagannathan, Sujatha et al. (2018) NuRD and CAF-1-mediated silencing of the D4Z4 array is modulated by DUX4-induced MBD3L proteins. Elife 7:
de Greef, Jessica C; Krom, Yvonne D; den Hamer, Bianca et al. (2018) Smchd1 haploinsufficiency exacerbates the phenotype of a transgenic FSHD1 mouse model. Hum Mol Genet 27:716-731
Campbell, Amy E; Belleville, Andrea E; Resnick, Rebecca et al. (2018) Facioscapulohumeral dystrophy: activating an early embryonic transcriptional program in human skeletal muscle. Hum Mol Genet 27:R153-R162
Mul, Karlien; Heatwole, Chad; Eichinger, Katy et al. (2018) Electrical impedance myography in facioscapulohumeral muscular dystrophy: A 1-year follow-up study. Muscle Nerve 58:213-218
Hendrickson, Peter G; Doráis, Jessie A; Grow, Edward J et al. (2017) Conserved roles of mouse DUX and human DUX4 in activating cleavage-stage genes and MERVL/HERVL retrotransposons. Nat Genet 49:925-934
Campbell, Amy E; Oliva, Jonathan; Yates, Matthew P et al. (2017) BET bromodomain inhibitors and agonists of the beta-2 adrenergic receptor identified in screens for compounds that inhibit DUX4 expression in FSHD muscle cells. Skelet Muscle 7:16

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