Novel sequence variants in dysferlin-deficient muscular dystrophy leading to mRNA decay and possible C2-domain misfolding

Item Type:	Article
Title:	Novel sequence variants in dysferlin-deficient muscular dystrophy leading to mRNA decay and possible C2-domain misfolding
Creators Name:	Wenzel, K. and Carl, M. and Perrot, A. and Zabojszcza, J. and Assadi, M. and Ebeling, M. and Geier, C. and Robinson, P.N. and Kress, W. and Osterziel, K.J. and Spuler, S.
Abstract:	Mutations in the gene encoding dysferlin (DYSF) cause the allelic autosomal recessive disorders limb girdle muscular dystrophy 2B and Miyoshi myopathy. It encompasses 55 exons spanning 150 kb of genomic DNA. Dysferlin is involved in membrane repair in skeletal muscle. We identified three families with novel sequence variants in DYSF. All affected family members showed limb girdle weakness and had reduced or absent dysferlin protein on immunohistochemistry. All exons of DYSF were screened by genomic sequencing. Five novel variants in DYSF were found: two missense mutations (c.895G>A and c.4022T>C), one 5' donor splice-site variant (c.855+1delG), one nonsense mutation (c.1448C>A), and a variant in the 3'UTR of DYSF (c.*107T>A). All alterations were confirmed by restriction enzyme analysis and not found in 400 control alleles. Nonsense mediated RNA decay or changes in the three-dimensional protein structure resulting in intracellular dysferlin aggregates and finally the lack of dysferlin protein were identified as consequences of the novel DYSF variants.
Keywords:	DYSF, Dysferlin, Limb girdle muscular dystrophy 2B, LGMD2B, mRNA decay
Source:	Human Mutation
ISSN:	1059-7794
Publisher:	Wiley
Volume:	27
Page Range:	599-600
Date:	June 2006
Official Publication:	https://doi.org/10.1002/humu.9424
PubMed:	View item in PubMed

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