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{\*\generator Microsoft Word 11.0.5604;}{\info{\title Clinical, genetic and epidemiological study of calpainopathy (LGMD2A) in Croatia}{\author Nina Canki-Klain}{\operator Nina Canki-Klain}{\creatim\yr2006\mo11\dy7\hr16\min6}
{\revtim\yr2006\mo11\dy7\hr16\min6}{\printim\yr2006\mo6\dy18\hr12\min36}{\version2}{\edmins2}{\nofpages1}{\nofwords388}{\nofchars2216}{\nofcharsws2599}{\vern24689}}\paperw11906\paperh16838\margl1417\margr1417\margt1417\margb1417 
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{\pntxtb (}{\pntxta )}}\pard\plain \qc \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid3763165 \fs24\lang2057\langfe1050\cgrid\langnp2057\langfenp1050 {\lang1033\langfe1050\langnp1033\insrsid3763165\charrsid6753098 CLINICAL}{
\lang1033\langfe1050\langnp1033\insrsid6753098\charrsid6753098 , GENETIC}{\lang1033\langfe1050\langnp1033\insrsid3763165\charrsid6753098  AND EPIDEMIOLOGICAL STUDY OF MAJOR AUTOSOMAL }{\lang1033\langfe1050\langnp1033\insrsid6753098\charrsid6753098 
RECESSIVE LIMB}{\lang1033\langfe1050\langnp1033\insrsid3763165\charrsid6753098  GIRDLE MUSCULAR DYSTROPHY}{\lang1033\langfe1050\langnp1033\insrsid6164841  (LGMD2)}{\lang1033\langfe1050\langnp1033\insrsid3763165\charrsid6753098  IN CROATIA
\par }\pard \qc \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid5262373 {\lang1033\langfe1050\langnp1033\insrsid5262373\charrsid6753098 Nina Canki-Klain
\par Croatian Institute for Brain }{\lang1033\langfe1050\langnp1033\insrsid6753098\charrsid6753098 Research and}{\lang1033\langfe1050\langnp1033\insrsid5262373\charrsid6753098  Department of Neurology, Zagreb University Medical School, Croatia
\par }\pard \ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid5971705 {\lang1033\langfe1050\langnp1033\insrsid5971705\charrsid6753098 
\par INTRODUCTION. }{\lang1033\langfe1050\langnp1033\insrsid8004972\charrsid6753098 In September 1998 we started a genetic and epidemiological study of muscular dystrophies (MDs) in Croatia. This report concerns results }{
\lang1033\langfe1050\langnp1033\insrsid6753098\charrsid6753098 obtained}{\lang1033\langfe1050\langnp1033\insrsid8004972\charrsid6753098  for }{\lang1033\langfe1050\langnp1033\insrsid5971705\charrsid6753098  LGMD2}{
\lang1033\langfe1050\langnp1033\insrsid8004972\charrsid6753098 ,}{\lang1033\langfe1050\langnp1033\insrsid5971705\charrsid6753098  a group of muscle diseases presenting great clinical and genetic heterogeneity making an etiologic 
diagnosis very difficult and clinically in majority of patients impossible. 
\par MATERIAL AND METHODS. Specific diagnostic strategy adapted to our country of 4, 4 million people was used. 
\par RESULTS. A 7-year long study showed that calpainopathy was the prevalen
t LGMD2. Analysis of 30 apparently unrelated families (47 patients) with calpain 3 (CAPN3) gene mutations and LGMD has discovered six different CAPN3 mutations: 550delA, R541W, P82L, delFWSAL, R49H, Y537X, accounting for 93% of CAPN3 chromosomes in the st
udied population. 550 delA was the }{\lang1033\langfe1050\langnp1033\insrsid12474593\charrsid6753098 most frequent}{\lang1033\langfe1050\langnp1033\insrsid5971705\charrsid6753098  mutation found on 43/60 (72%) }{
\lang1033\langfe1050\langnp1033\insrsid6753098\charrsid6753098 analyzed}{\lang1033\langfe1050\langnp1033\insrsid5971705\charrsid6753098 
 CAPN3 chromosomes; other five mutations ranged from 8 to 2%. In 26 families two CAPN3 alleles were identified. In remaining 4 families with only one known CAPN3 allele, 550delA was present in 3 of 4 alleles, and P82L in one.}{
\lang1033\langfe1050\langnp1033\insrsid16215744\charrsid6753098  The second, most common LGMD2 seems to be type 2I}{\lang1033\langfe1050\langnp1033\insrsid14811835\charrsid6753098  caused by mutation in fukutin related protein (FKRP)}{
\lang1033\langfe1050\langnp1033\insrsid16215744\charrsid6753098 . Since introduc}{\lang1033\langfe1050\langnp1033\insrsid14811835\charrsid6753098 tion of}{\lang1033\langfe1050\langnp1033\insrsid16215744\charrsid6753098  direct analysis }{
\lang1033\langfe1050\langnp1033\insrsid6753098\charrsid6753098 of C826A}{\lang1033\langfe1050\langnp1033\insrsid16215744\charrsid6753098 , a year ago, we found five unrelated f}{\lang1033\langfe1050\langnp1033\insrsid14811835\charrsid6753098 amilies 
with identical C826A mutation }{\lang1033\langfe1050\langnp1033\insrsid3345757 that}{\lang1033\langfe1050\langnp1033\insrsid6753098\charrsid6753098  results}{\lang1033\langfe1050\langnp1033\insrsid14811835\charrsid6753098 
 in the substitution of isoleucin for leucin. }{\lang1033\langfe1050\langnp1033\insrsid15074819\charrsid6753098 
Three patients from two unrelated, informative families are affected by presumed MM/LGMD2B. Haplotype analysis using microsatellites flanking the dysferlin gene and non-invasive western blot}{\lang1033\langfe1050\langnp1033\insrsid12406542  (WB) analysis}
{\lang1033\langfe1050\langnp1033\insrsid11879751\charrsid6753098  of dysferlin}{\lang1033\langfe1050\langnp1033\insrsid12406542  (DYSF) gene}{\lang1033\langfe1050\langnp1033\insrsid11879751\charrsid6753098 
 from peripheral blood confirmed diagnosis, but mutation(s) }{\lang1033\langfe1050\langnp1033\insrsid353525 is/}{\lang1033\langfe1050\langnp1033\insrsid11879751\charrsid6753098 are still unidentified.}{
\lang1033\langfe1050\langnp1033\insrsid15074819\charrsid6753098 \line }{\lang1033\langfe1050\langnp1033\insrsid5971705\charrsid6753098 DISCUSSION. }{\lang1033\langfe1050\langnp1033\insrsid6753098\charrsid6753098 Surprisingly}{
\lang1033\langfe1050\langnp1033\insrsid9900358\charrsid6753098 , we have identified any }{\lang1033\langfe1050\langnp1033\insrsid6753098\charrsid6753098 sarcoglycanopathy probably}{\lang1033\langfe1050\langnp1033\insrsid9900358\charrsid6753098 
 because of sampling bias}{\lang1033\langfe1050\langnp1033\insrsid6840102\charrsid6753098  (small no of children)}{\lang1033\langfe1050\langnp1033\insrsid9900358\charrsid6753098  and limited methodology}{
\lang1033\langfe1050\langnp1033\insrsid6840102\charrsid6753098  (lack of biopsy and WB of different proteins)}{\lang1033\langfe1050\langnp1033\insrsid9900358\charrsid6753098 . }{\lang1033\langfe1050\langnp1033\insrsid5971705\charrsid6753098 
Because of high frequency of healthy 550delA heterozygotes (1 in 133) and relative frequency of healthy heterozygotes for C826A mutation, which is responsible for LGMD2I (1 in 524) in our general population, we}{
\lang1033\langfe1050\langnp1033\insrsid3805091  need to know both allele to confirm the diagnosis of LGMD2A and 2I.}{\lang1033\langfe1050\langnp1033\insrsid5971705\charrsid6753098 
\par CONCLUSION. To study natural history of }{\lang1033\langfe1050\langnp1033\insrsid6840102\charrsid6753098 any LGMD2 }{\lang1033\langfe1050\langnp1033\insrsid5971705\charrsid6753098 
both alleles must be known as well as genetically homogenous groups should be follow up according to as simple as possible protocol.
\par 
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\par }}