Journal
NATURE GENETICS
Volume 39, Issue 9, Pages 1134-1139Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng2086
Keywords
-
Categories
Ask authors/readers for more resources
Centronuclear myopathies are characterized by muscle weakness and abnormal centralization of nuclei in muscle fibers not secondary to regeneration. The severe neonatal X- linked form ( myotubular myopathy) is due to mutations in the phosphoinositide phosphatase myotubularin ( MTM1)(1), whereas mutations in dynamin 2 ( DNM2) have been found in some autosomal dominant cases(2). By direct sequencing of functional candidate genes, we identified homozygous mutations in amphiphysin 2 ( BIN1) in three families with autosomal recessive inheritance. Two missense mutations affecting the BAR ( Bin1/ amphiphysin/ RVS167) domain disrupt its membrane tubulation properties in transfected cells, and a partial truncation of the C- terminal SH3 domain abrogates the interaction with DNM2 and its recruitment to the membrane tubules. Our results suggest that mutations in BIN1 cause centronuclear myopathy by interfering with remodeling of T tubules and/ or endocytic membranes, and that the functional interaction between BIN1 and DNM2 is necessary for normal muscle function and positioning of nuclei.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available