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Re: New gene/mutation found to causes a form of MTM/CNM

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  • Ray
    I thought that everyone knew that partial truncation of the C- terminal SH3 domain abrogates the interaction with DNM2 and its recruitment to the membrane
    Message 1 of 2 , Aug 7, 2007
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      I thought that everyone knew that partial truncation of the C-
      terminal SH3 domain abrogates the interaction with DNM2 and its
      recruitment to the membrane tubules...I mean, tell us something that
      we don't already know...or, alternatively, do they have that abstract
      in English?? :0) Nevermind, I'll just take their word for it and put
      it in my 'Things That are Probably Good' folder...




      --- In Myotubular_Myopathy@yahoogroups.com, "patsarah2006"
      <patsarah@...> wrote:
      >
      > It seems that finally at least one gene has been identified for
      > autosomal recessive centronuclear myopathy (AR-CNM). But out of 55
      > individuals with presumed AR-CNM, only 4 tested positive at this
      > gene, suggesting that other, still unidentified genes are
      responsible
      > for most cases of AR-CNM. The research may shed light on the
      > mechanisms for all forms of MTM/CNM.
      >
      > The authors(mostly in France): Nicot AS, Toussaint A, Tosch V,
      Kretz
      > C, Wallgren-Pettersson C, Iwarsson E, Kingston H, Garnier JM,
      > Biancalana V, Oldfors A, Mandel JL, Laporte J.
      >
      > Title of the article: Mutations in amphiphysin 2 (BIN1) disrupt
      > interaction with dynamin 2 and cause autosomal recessive
      > centronuclear myopathy.
      >
      > Journal: Nature Genetics. August 5, 2007.
      >
      > Below is the abstract (summary) for the article. Pretty technical
      > stuff:
      >
      > 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), whereas mutations in dynamin 2 (DNM2) have been found in
      some
      > autosomal dominant cases. 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.
      > ++++++++++++++++++
      > -Pat in New Jersey
      >
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