Human Molecular Genetics, Vol 7, 135-139, Copyright © 1998 by Oxford University Press
K Small and ST Warren
Emery-Dreifuss muscular dystrophy (EMD) is an X-linked disorder
characterized by contractures, progressive weakness and cardiomyopathy. EMD
is caused by mutations in the 2 kb emerin gene that is located within human
Xq28. Emerin is immediately distal to the 26 kb filamin gene, and flanking
the filamin-emerin region are two large inverted repeats. This entire
region previously has been found to be inverted in approximately 20% of X
chromosomes, presumably mediated by the inverted repeats. Only one complete
emerin deletion has been reported previously. It was found to be due to a
complex rearrangement involving the inverted repeats which partially
duplicated filamin. We report here two additional EMD patients who have
large deletions of 20 and 34 kb, respectively. Unlike the previously
reported deletion, these deletions appear to be simple deletions, with each
breakpoint junction showing only 2 bp of overlap, suggesting an end-joining
mechanism. However, the two deletions were found on each of the two
inverted backgrounds. The 20 kb deletion includes the entire emerin gene
and extends well into most of the distal inverted repeat. In contrast, the
34 kb deletion occurs on the inverted X chromosome and extends centromeric,
well beyond the proximal inverted repeat. In addition, at least three
nearby putative genes detected by previous sequence analysis are deleted
among these patients but without obvious deviation from a typical EMD
phenotype. Similarly to the previously reported deletion, filamin remains
intact in these two deletions. All three deletions involve distinct
breakpoints within the 4.7 kb filamin-emerin intergenic region, suggesting
that loss of filamin is a lethal event. Thus, the close proximity of
filamin to emerin may place constraints upon potential emerin deletions and
probably accounts for the rarity of complete emerin deletions in EMD
patients.
ARTICLES
Emerin deletions occurring on both Xq28 inversion backgrounds
Howard Hughes Medical Institute and Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA.
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