Thursday, October 22, 2009

FSHD-Europe - the Voice of Europe

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Last FSHD publication (Abstract)

Eur J Hum Genet. 2009 Oct 7.

Comprehensive expression analysis of FSHD candidate genes at the mRNA and protein level.

Klooster R
, Straasheijm K
, Shah B
, Sowden J
, Frants R
, Thornton C
, Tawil R
, van der Maarel S
. Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.

In facioscapulohumeral muscular dystrophy (FSHD) the majority of patients carry a D4Z4 macrosatellite repeat contraction in the subtelomere of chromosome 4q.

Several disease mechanisms have been proposed to explain how repeat contraction causes muscular dystrophy. All proposed mechanisms foresee a change from a closed to a more open chromatin structure followed by loss of control over expression of genes in or proximal to D4Z4.

Initially, a distance and residual repeat size-dependent upregulation of the candidate genes FRG2, FRG1 and ANT1 was observed, but most successive expression studies failed to support transcriptional upregulation of 4qter genes. Moreover, chromatin studies do not provide evidence for a cis-spreading mechanism operating at 4qter in FSHD. In part, this inconsistency may be explained by differences in the techniques used, and the use of RNA samples obtained from different muscle groups.

The aim of this study is to comprehensively and uniformly study the expression of the FSHD candidate genes FRG1, FRG2, CRYM, ANT1, ALP, PITX1 and LRP2BP at the RNA and protein level in identically processed primary myoblasts, myotubes and quadriceps muscle.

Expression was compared between samples obtained from FSHD patients and normal controls with samples from myotonic dystrophy type 1 patients as disease controls. No consistent changes in RNA or protein expression levels were observed between the samples. The one exception was a selective increase in FRG2 mRNA expression in FSHD myotubes.

This study provides further evidence that there is no demonstrable consistent, large magnitude, overexpression of any of the FSHD candidate genes.


. Muscular Dystrophies Campaign (MDC) : UK
. FSHD Stichting : Netherlands
. Unione Italiana Lotta alla Distrofia Muscolare (UILDM) : Italy
. Amis FSH Europe : France


Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common dystrophies (1 case in 14,000 individuals).
FSHD is characterized by a and progressive loss of motion autonomy. Its infantile form (iFSHD) is considered the most severe form of the disease.
The origin of FSHD has not yet been identified, nor has a therapy been found for the moment.

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