8ihE\lifgj`hl`Xki)''02-.( 1(')$('+
(')
:c`e`ZXc&JZ`\ek`ÔZefk\
D@KF:?FE;I@8C8CK<I8K@FEJ@E;PE8D@E
)$I<C8K<;:<EKIFEL:C<8IDPFG8K?P
<[dXiQXefk\c`
(#EXaXM\i^Xe`
)#PmXe:Xdgfj
)#DXi`qMX`eqf]
*#
8ZXipJ%9%Fc`m\`iX
(#8c\jjXe[iX[Ë8qqf
)8CK<I8xÃ<JD@KF:FE;I@8@JE8D@FG8K@8:<EKIFEL:C<8II<C8:@FE8;8J8;@E8D@E8)
(;\gXikd\ekf]E\lifcf^p#LE@=<JG$<GD#JfGXlcfJG#9iXq`c2);\gXikd\ekf]>\e\k`ZjXe[Kldfi:\cc9`fcf^p#Jk%Al[\:_`c[i\eËjI\j\XiZ_?fjg`kXc#
D\dg_`j#LJ82*?ldXe>\efd\I\j\XiZ_:\ek\i#@9$LJG#JfGXlcfJG#9iXq`c%<%Q%Xe[8%[Ë8%Xi\jlggfik\[Ypk_\EXk`feXc@ejk`klk\jf]?\Xck_>iXek
8I'+00/-.#k_\:XeZ\i:\ek\i:FI< jlggfik^iXek:8')(.-,#k_\8jj`j`=fle[Xk`fef]D\dg_`j#Xe[k_\8d\i`ZXeC\YXe\j\Jpi`Xe8jjfZ`Xk\[ :_Xi`k`\j8CJ8: %D%M%`jjlggfik\[Yp=8G<JGXe[:EGh%
I\Z\`m\[(.J\gk\dY\i)''/%8ZZ\gk\[();\Z\dY\i)''/%
;i%<[dXiQXefk\c`Æ;\gXikd\ekf]E\lifcf^p&LE@=<JG$<GD$IlX9fklZXkl.+'$'+')*$0''JfGXlcfJG$9iXj`c%<$dX`c1qXefk\c`7k\iiX%Zfd%Yi :\ekifelZc\XidpfgXk_p:ED `jZc`e`ZXccpZ_XiXZ$
k\i`q\[Yp[`]]lj\`emfcm\d\ekf]jb\c\kXcdljZc\j#n`k_ fej\kdX`ecp`e\XicpZ_`c[_ff[Xe[Xjcfncpgif^i\jj`m\ Zflij\%K_\YXj`Z_`jkfcf^`ZXcXYefidXc`k`\j`edljZc\ Y`fgj`\jXi\X_`^_g\iZ\ekX^\f]Z\ekiXccpcfZXk\[el$ Zc\`f]dljZc\ÔY\ij#iX[`XcXiiXe^\d\ekf]jXiZfgcXjd`Z jkiXe[jXifle[k_\Z\ekiXcelZc\`#Xe[gi\[fd`eXeZ\Xe[ _pgfkifg_pf]kpg\(ÔY\ij($*%K_i\\]fidjf]k_\[`j\Xj\ _Xm\Y\\ei\Zf^e`q\[k_Xk[`]]\i`eX^\f]fej\kXe[j\m\i$ `kpf]k_\jpdgkfdj1K_\j\m\i\O$c`eb\[dpfklYlcXidp$ fgXk_p#ZXlj\[YpdlkXk`fej`ek_\DKD(^\e\2k_\Z_`c[$ _ff[fej\k]fid2Xe[k_\alm\e`c\&X[lckfej\k]fidk_Xk ]lccpdXe`]\jkj[li`e^k_\k_`i[[\ZX[\f]c`]\%@ek_\alm\$ e`c\&X[lckfej\k]fid#dfjkf]k_\]Xd`c`\j_Xm\XeXlkf$ jfdXc[fd`eXek`e_\i`kXeZ\#Xe[gXk`\ekjgi\j\ekn`k_X jcfncpgif^i\jj`m\[`j\Xj\#Ylkn`k_d`c[Zc`e`ZXcdXe`]\j$ kXk`fej)%K_`j]fid_XjY\\eXjjfZ`Xk\[n`k_dlkXk`fej`e k_\[peXd`e)^\e\;ED)+%Dfi\i\Z\ekcp#E`Zfk\kXc%, [\jZi`Y\[`ek_i\\:ED]Xd`c`\jn`k_XlkfjfdXci\Z\jj`m\ `e_\i`kXeZ\dlkXk`fej`eXdg_`g_pj`e)^\e\#n_`Z_[`j$ ilgkk_\`ek\iXZk`fen`k_[peXd`e)gifk\`e%
N\_Xm\efn`[\ek`Ô\[XeX[lck$:EDgXk`\ekn`k_
dlkXk`fe`e;ED)Xe[fm\ikd`kfZ_fe[i`XcZ_Xe^\j`e
dljZc\Y`fgjp%
:8J<
8,'$p\Xi$fc[dXc\#]ifdXcXi^\9iXq`c`Xe]Xd`cp#gi\j\ek$ \[j`eZ\k_\X^\f]*'n`k_jcfncpgif^i\jj`m\dljZc\n\Xbe\jj XjjfZ`Xk\[n`k_`dgX`i\[ZXgXZ`kpkfjkXe[lg#ileXe[Zc`dY k_\jkX`ij=`^(#@@@$- %:c`e`ZXc\oXd`eXk`feZfeÔid\[n\Xbe\jj gi\[fd`eXekcp`ek_\[`jkXcgXikf]k_\c`dYjKXYc\ %K_\>fn$ \ijËj`^eXcnXjgi\j\ek%?\Zflc[efknXcbfe_`j_\\c%8kifg_p f]k_\c`dYjnXj\m`[\ek#\jg\Z`Xccp`ek_\[`jkXcgXikj#Xjn\cc Xjk\e[fe_pgfi\Õ\o`Xn`k_efidXcdljZlcXikfelj%K_\i\nXj efefk`Z\XYc\n\Xbe\jjf]]XZ`XcfifZlcXidfm\d\ek2Xe[gkf$ j`jnXjXYj\ek%K_\gXk`\ekËjdfjkZfej`jk\ekZfdgcX`eknXj\Xjp ]Xk`^l\\m\e[li`e^i\^lcXi[X`cpXZk`m`kp%
Fk_\i]fliX]]\Zk\[d\dY\ijf]_`j]Xd`cpn\i\Xcjf\oXd$ `e\[=`^( KXYc\ %K_\j\gXk`\ekj_X[j`d`cXiZfdgcX`ekjf]]X$ k`^l\#dljZc\gX`eXe[ZiXdgj%8ccgXk`\ekjgi\j\ek\[Xjcfncp gif^i\jj`m\[`j\Xj\#Xe[Zflc[efknXcbfek_\`i_\\cj%8ccgX$ k`\ekj_X[efidXcfZlcXidfm\d\ekj%EfidXcdljZlcXikfelj n`k__pgfi\Õ\o`XnXjfYj\im\[`eXccX]]\Zk\[gXk`\ekj%GXk`\ekj @@$-#@@@$,#Xe[@M$)gi\j\ek\[XZc\Xi[`jkXcXkifg_pf]k_\c`dYj# \jg\Z`Xccp`ek_\cfn\ic\^j%E\feXkXcdXe`]\jkXk`fejjlZ_Xjd`c[ _pgfkfe`X#jlZk`feXe[Zipn\Xbe\jjn\i\[\jZi`Y\[fecp]fi k_\gXk`\ek@@@$,2_fn\m\ik_\dfkfi[\m\cfgd\eknXjefidXc% ;\ckf`[dljZc\Y`fgjp]ifdgXk`\ek@@@$-#g\i]fid\[Xkk_\ X^\f],'#j_fn\[`eZi\Xj\[eldY\if]Z\ekiXcelZc\`dfi\k_Xe
8ihE\lifgj`hl`Xki)''02-.(
('* :\ekifelZc\XidpfgXk_p1d`kfZ_fe[i`XcXck\iXk`fej QXefk\c`\kXc%
KXYc\%:c`e`ZXc[XkX]ifd,gXk`\ekjn`k_;ED)$:ED]ifdk_\jXd\]Xd`cp%
:Xj\ J\o& X^\p
Fej\k p
=`ijk jpdgkfdj
:fdgcX`ej =XZ`Xc dljZc\j
Gifo`dXc dfm\d\ekj
DI:
;`jkXc dfm\d\ekj
DI:
:\im`ZXc dfm\d\ekj
DI:
Fjk\fjb\c\kXc Z_Xe^\j
@@$- =&-+ +' =Xk`^XY`c`kp Xe[n\Xbe\jj
]finXcb`e^
DljZc\gX`e# ]Xk`^l\# ZiXdgj
D`c[ [pjg_X^`X
?`gÕ\o`fe +" #c\^ \ok\ej`fe
+" #c\^ X[[lZk`fe+
8ebc\ [fij`Õ\o`fe Xe[\m\ij`fe +$ #Xebc\ Õ\o`feXe[ `em\ij`fe+"
=c\o`fe+ G\jZXmlj \hl`efmXilj#
ni`jkXe[ 8Z_`cc\j i\kiXZk`fe
@@@$, =&*, 6 NXcb n\Xbe\jj%
E\feXkXc _pgfkfe`X# n\XbjlZk`fe
Xe[Zip%
DljZc\gX`e# ]Xk`^l\# ZiXdgj
Gkfj`jj`eZ\ Z_`c[
?`gÕ\o`fe +" #c\^ \ok\ej`fe+"
8ebc\ [fij`Õ\o`fe Xe[\m\ij`fe + #Xebc\ Õ\o`feXe[ `em\ij`fe+"
ec ef
@@@$- D&,' *' N\Xbe\jj =Xk`^l\ DXjk`ZXkfip dljZc\j Xkifg_p
8idXY[lZk`fe + Xe[ \ok\ej`fe+ # c\^\ok\ej`fe$ Õ\o`fe+ Xe[ X[[lZk`fe+
8ebc\ [fij`Õ\o`fe
+$ #Xebc\ \m\ij`fe+$ # ]ffkgcXekXi Õ\o`fe+ Xe[ni`jk \ok\ej`fe$ Õ\o`fe+
=c\o`feXe[ \ok\ej`fe+
ef
@@@$/ =&*) 6 6 =Xk`^l\# ZiXdgj
?`^_$XiZ_\[ gXcXk\
?`gÕ\o`fe +" #Xid \ok\ej`fe+"
8ebc\ [fij`Õ\o`fe+
=c\o`fe+ 8Z_`cc\j i\kiXZk`fe
@M$) =&)' 6 6 ef ec ?`gÕ\o`fe
+" #Xid \ok\ej`fe+"
8ebc\ [fij`Õ\o`fe+
ec ef
8^\i\]\ijkfk_\k`d\f]\oXd`eXk`fe2DI:#D\[`ZXcI\j\XiZ_:fleZ`cjZXc\2"#gi\j\ek2Æ#XYj\ek2p#p\Xij2ec#efidXc2=#]\dXc\2D#dXc\2;ED)$:ED# [peXd`e)$i\cXk\[Z\ekifelZc\XidpfgXk_p%
8ihE\lifgj`hl`Xki)''02-.(
('+
:\ekifelZc\XidpfgXk_p1d`kfZ_fe[i`XcXck\iXk`fej QXefk\c`\kXc%
/'f]k_\ÔY\ij #`ek\ej\mXi`Xk`fe`eÔY\ij`q\#df[\iXk\`e$ Zi\Xj\f]k_\\e[fdpj`XcXe[g\i`dpj`XcZfee\Zk`m\k`jjl\Xe[ `ek\ej\g\i`]XjZ`ZlcXi]Xk`eÔckiXk`fe=`^)8 %K_\_`jkfZ_\d`ZXc jkl[pi\m\Xc\[gi\[fd`eXeZ\Xe[_pgfkifg_pf]kpg\(ÔY\ij% Jgfb\$c`b\Xgg\XiXeZ\nXjfYj\im\[`edfjkf]k_\ÔY\ij=`^ )9 %8Yflk+f]k_\ÔY\ijj_fn\[XiX^^\[$i\[Xjg\Zk=`^): % 8[[`k`feXccp#k_\i\n\i\ÔY\ijn`k_`eZi\Xj\[J;?XZk`m`kp=`^ ); Xe[i\[lZ\[fiXYj\ek:FOXZk`m`kpXYflk, =`^)<Æ= % @eÕXddXk`feXe[e\Zifj`jn\i\efkfYj\im\[%K_\dljZc\Y`$ fgjp]ifdXefk_\i]Xd`cpd\dY\i@@@$, #g\i]fid\[Xkk_\X^\ f]*,#j_fn\[kpg`ZXcZ_XiXZk\i`jk`Zjf]:ED#YlkefiX^^\[$i\[ ÔY\ij#J;?gfj`k`m\ÔY\ijfi:FO[\ÔZ`\ekÔY\ij%
K_\\ofejXe[`ekife$\ofeYfle[Xi`\j]ifdk_\d`[[c\[f$ dX`ef]k_\;ED)^\e\n\i\j\hl\eZ\[#Xe[X_\k\ifqp^flj d`jj\ej\dlkXk`fe`e\ofe(((*0*:ÆK #n_`Z_i\jlckj`ek_\Xd`$ efXZ`[jlYjk`klk`feI+-,N#nXj`[\ek`Ô\[`egXk`\ekj@@$-#@@@$,# @@@$-#@@@$/Xe[@M$)%
K_\dljZc\Y`fgj`\jXe[k_\;E8]ifdk_\gXk`\ekjn\i\ fYkX`e\[n`k_`e]fid\[Zfej\ek]fccfn`e^gifkfZfcjXggifm\[ Ypk_\\k_`ZXcZfdd`kk\\]ifdk_\@ejk`klk`fe%
;@J:LJJ@FE
N\i\gfik_\i\XZXj\f]X[lckfej\k:EDn`k_dlkX$ k`fe`ek_\;ED)^\e\Xe[X[[`k`feXc_`jkfcf^`ZXcÔe[`e^j kpg`ZXccpj\\e`ed`kfZ_fe[i`Xc[`j\Xj\j%
FecpX]\ni\gfikjXi\gi\j\ek`ek_\c`k\iXkli\[\$ jZi`Y`e^d`kfZ_fe[i`XcZ_Xe^\j`e:EDgXk`\ekj%@efe\ gXk`\ek#ZipjkXcc`e\`eZclj`fejn\i\]fle[`ed`kfZ_fe$ [i`XX[aXZ\ekkfk_\Z\ekiXc`q\[elZc\`-%@eXefk_\iZXj\# d`kfZ_fe[i`XcXYefidXc`k`\j#`eZcl[`e^i\[lZk`fef]k_\ eldY\if]Z\ekiXcXe[jlYjXiZfc\ddXcd`kfZ_fe[i`X# i\[lZk`fef]Zi`jkX\#Xe[d`kfZ_fe[i`Xci\deXekjn`k_`e cpjfjfd\j#n\i\fYj\im\[.#Xe[EXldXee\kXc%/[\jZi`Y\[ knfkpg`ZXcX[lck:EDgXk`\ekjn`k_iX^^\[$i\[ÔY\ij Xe[ÔY\ijn`k_XYj\eZ\f]:FOjkX`e`e^`ek_\dljZc\Y`$ fgjp%8ck_fl^_efdfc\ZlcXiXeXcpj\jn\i\[fe\feXep f]k_\j\gXk`\ekj#k_\`i_`jkfcf^`ZXcXck\iXk`fejn\i\j`d`$ cXikfk_fj\[\jZi`Y\[`e:EDgXk`\ekjZXiip`e^dlkXk`fej `ek_\;ED)^\e\#`%\%ÔY\ikpg\mXi`XY`c`kp#kpg\(Xkif$ g_pXe[jgfb\$c`b\Xgg\XiXeZ\+%=lik_\idfi\#k_\j\gX$ k`\ekjXcjf_X[XcXk\fej\k]fidf]k_\[`j\Xj\%9Xj\[fe fliÔe[`e^j#n\Y\c`\m\k_XkXcjfk_fj\\XicpZXj\jd`^_k _Xm\ZXii`\[dlkXk`fej`ek_\;ED)^\e\#`e[`ZXk`e^k_Xk
k_\ZfdY`e\[fZZlii\eZ\f]:EDn`k_;ED)dlkXk`fej
Xe[d`kfZ_fe[i`XcZ_Xe^\jZflc[Y\dfi\]i\hl\ekk_Xe i\Zf^e`q\[lek`cefn%Dfi\i\Z\ekcp#iX^^\[i\[]`Y\ij n\i\`[\ek`Ô\[`ek_\dljZc\Y`fgjp]ifdXgXk`\ekn`k_
;ED)$i\cXk\[:ED;ED)$:ED 0%
N\Zflc[jg\ZlcXk\k_XkXck\i\[;ED)gifk\`edXb\j k_\jb\c\kXcdljZc\f]:EDgXk`\ekjdfi\gife\kf[\m\c$ fgXd`kfZ_fe[i`Xc[pj]leZk`feXjk_\pX^\%K_`jZflc[\o$ gcX`ek_\cXZbf]d`kfZ_fe[i`XcZ_Xe^\j`eXefk_\iX]]\Zk$
\[d\dY\if]k_\jXd\]Xd`cp#n_fnXjY`fgj`\[Xkk_\ X^\f]*,%@eX[[`k`fe#n\ZXeefk\oZcl[\`ek\i]Xd`c`XcmXi`$ XY`c`kp#n_`Z_`jZfddfecpfYj\im\[`edljZc\[`j\Xj\j%
9`kfle\kXc%+[\dfejkiXk\[k_Xk`e;ED)$:EDk_\
;ED)gifk\`egi\j\ekjXeXY\iiXekZ\ekifjfdXccfZXc`qX$ k`fe`em`kif#`e[`ZXk`e^k_Xk;ED)dlkXk`fejd`^_kZXlj\ :EDYp`ek\i]\i`e^n`k_Z\ekifjfd\]leZk`fe%;peXd`ej Xi\cXi^\>KGXj\j`emfcm\[`ed\dYiXe\kiX]ÔZb`e^k_Xk XZkXjd\Z_XefZ_\d`ZXcjZX]]fc[`e^dfc\Zlc\jk_XkZXe _p[ifcpq\>KGkfXck\iY`fcf^`ZXcd\dYiXe\j('%8dfe^k_\ [peXd`e]Xd`cp#k_\(''$b;X>KGXj\;ED)`jbefnekfY\ `emfcm\[`e\e[fZpkfj`jXe[d\dYiXe\kiX]ÔZb`e^((#XZk`e i\fi^Xe`qXk`fe()#Xe[Z\ekifjfd\Zf_\j`fe(*%=lik_\idfi\# [peXd`e$i\cXk\[>KGXj\_XjY\\ejl^^\jk\[kfY\`emfcm\[ `ek_\gifZ\jj\jf]d`kfZ_fe[i`XcÔjj`feXe[]lj`fe(+#(,# Yfk_f]n_`Z_Xi\befnekfgcXpXb\pifc\`eZ\cc[`m`j`fe Xe[[`]]\i\ek`Xk`fe%:fej`[\i`e^k_\YifX[iXe^\f]Z\cclcXi d\Z_Xe`jdj`en_`Z_;ED)`j`emfcm\[#`k`jZfeZ\`mXYc\ k_XkXeXck\i\[;ED)gifk\`eZflc[Xcjf`ek\i]\i\n`k_k_\ Zfii\Zk]fidXk`feXe[&fi]leZk`fef]k_\d`kfZ_fe[i`X`e X]]\Zk\[gXk`\ekj#\jg\Z`Xccp[li`e^k_\X^`e^%N\ZfeZcl[\ k_XkdljZc\Y`fgjp]ifd;ED)$:EDgXk`\ekjj_flc[ Y\`em\jk`^Xk\[]fiXjjfZ`Xk\[d`kfZ_fe[i`XcZ_Xe^\j%
I<=<I<E:<J
1. Spiro AJ, Shy GM, Gonatas NK. Myotubular myopathy. Arch Neurol 1966;14:1-14.
2. Goebel HH, Meinck HM, Reinecke M, Schimrigk K, Mielke U. Centro-nuclear myopathy with special consideration of the adult form. Eur Neurol 1984;23:425-434.
3. Zanoteli E, Oliveira ASB, Schmidt B, Gabbai AA. Centronuclear myo-pathy: clinical aspects of ten Brazilian patients with childhood onset. J Neurol Sci 1998;158:76-82.
4. Bitoun M, Maugenre S, Jeannet PY, et al. Mutations in dynamin 2 cause dominant centronuclear myopathy. Nat Genet 2005;37:1207-1209. 5. Nicot AS, Toussaint A, Tosch V, et al. Mutations in amphiphysin 2
(BIN1) disrupt interaction with dynamin 2 and cause autosomal reces-sive centronuclear myopathy. Nat Genet 2007;39:1134-1139. 6. Canal N, Comi GC, Comola M, Testa D, Mora M, Cornelio F.
Centronu-clear myopathy with unusual mitochondrial abnormalities. Clin Neu-ropathol 1985;4:23-27.
7. Hulsmann N, Gullotta F, Okur H. Cytopathology of an unusual case of centronuclear myopathy: light- and electron-microscopic investiga-tions. J Neurol Sci 1981;50:311-333.
8. Naumann M, Reiners K, Gold R, et al. Mitochondrial dysfunction in adult-onset myopathies with structural abnormalities. Acta Neuro-pathol 1995;89:152-157.
3LUUD/'XEURYVN\$%LWRXQ0HWDO5DJJHGUHGÀEUHVÀQGLQJLQPXV
-cle biopsy of dynamin 2-related centronu-clear myopathy. Neuromuscul Disord 2007;17:881-882.
10. Praefcke GJ, McMahon HT. The dynamin superfamily: universal
PHPEUDQHWXEXODWLRQDQGÀVVLRQPROHFXOHV"1DW5HY0RO&HOO%LRO
2004;5:133-147.
11. Jones SM, Howell KE, Henley JR, Cao H, McNiven MA. Role of dy-namin in the formation of transport vesicles from the trans-Golgi net-work. Science 1998;279:573-577.
12. Orth JD, McNiven MA. Dynamin at the actin-membrane interface. Curr Opin Cell Biol 2003;15:31-39.
13. Thompson HM, Cao H, Chen J, Euteneuer U, McNiven MA. Dynamin 2 binds gamma-tubulin and participates in centrosome cohesion. Nat Cell Biol 2004;6:335-342.
14. Barsoum MJ, Yuan H, Gerencser AA, et al. Nitric oxide-induced
mito-FKRQGULDOÀVVLRQLVUHJXODWHGE\G\QDPLQUHODWHG*73DVHVLQQHXURQV
EMBO 2006;25:3900-3911.
