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{\pntxtb (}{\pntxta )}}\pard\plain \ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs24\lang2057\langfe1050\cgrid\langnp2057\langfenp1050 {\f36\insrsid12597031\charrsid8023511 
Clinical, genetic and epidemiological study of calpainopathy (LGMD2A) in Croatia}{\f36\insrsid12731558\charrsid8023511 
\par }\pard \qc \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid12667738 {\f36\insrsid12667738 Nina Canki-Klain}{\f36\insrsid154335\charrsid12667738 
\par }{\f36\insrsid12667738\charrsid12667738 Croatian Institute for Brain Research  and Department of Neurology, Zagreb University Medical School, Croatia}{\f36\insrsid12667738\charrsid12667738 
\par }\pard \ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\f36\insrsid154335\charrsid8023511 INTRODUCTION. Autosomal recessive limb-girdle muscular dystrophies (LGMD2) form a group of muscle diseases presenting}{
\f36\insrsid6059516\charrsid8023511  great clinical and genetic heterogeneity }{\f36\insrsid8023511\charrsid8023511 making an}{\f36\insrsid6059516\charrsid8023511  etiologic diagnosis very difficult and }{\f36\insrsid8023511\charrsid8023511 clinically}{
\f36\insrsid6059516\charrsid8023511  in majority of patients impossible.}{\f36\insrsid6319005\charrsid8023511  In }{\f36\insrsid4803269 September}{\f36\insrsid6319005\charrsid8023511  1998 we started }{\f36\insrsid1649150 a }{
\f36\insrsid6319005\charrsid8023511 genetic and epidemiological study of muscular dystrophies }{\f36\insrsid3750365 (MDs) }{\f36\insrsid6319005\charrsid8023511 in Croatia.
\par MATERIAL AND }{\f36\insrsid8023511\charrsid8023511 METHODS. Specific}{\f36\insrsid6319005\charrsid8023511  diagnostic strategy adapted to our country of 4}{\f36\insrsid5982720 , 4}{\f36\insrsid6319005\charrsid8023511  }{
\f36\insrsid8023511\charrsid8023511 million}{\f36\insrsid6319005\charrsid8023511  people was used.}{\f36\insrsid7820075\charrsid8023511  }{\f36\insrsid5982720 
\par }{\f36\insrsid16059518\charrsid8023511 RESULTS. A 7-year long study showed that calpainopathy was the prevalent}{\f36\insrsid5982720  }{\f36\insrsid12544884\charrsid8023511 LGMD2}{\f36\insrsid16059518\charrsid8023511 . A}{
\f36\insrsid9986626\charrsid8023511 nalysis of 30}{\f36\insrsid16059518\charrsid8023511  }{\f36\insrsid5982720 apparently }{\f36\insrsid16059518\charrsid8023511 unrelated families}{\f36\insrsid8212682  (47 patients)}{\f36\insrsid16059518\charrsid8023511 
 with calpain 3 (CAPN3) gene mutations and LGMD has discovered six different CAPN3 mutations:}{\f36\insrsid4413771\charrsid8023511  550delA, R541W, P82L, delFWSAL, R49H, Y537X, accounting 
for 93% of CAPN3 chromosomes in the studied population. 550 delA was the }{\f36\insrsid9986626\charrsid8023511 prevalent}{\f36\insrsid4413771\charrsid8023511  mutation found on 43/60 (}{\f36\insrsid9986626\charrsid8023511 72%) analysed CAPN3 chromosomes;}
{\f36\insrsid4413771\charrsid8023511  other five mutations ranged from 8 to 2%. In 26 families two CAPN3 alleles were identified. In remaining 4 families }{\f36\insrsid9986626\charrsid8023511 with}{\f36\insrsid4413771\charrsid8023511  only one }{
\f36\insrsid5519687 known }{\f36\insrsid9986626\charrsid8023511 CAPN3 }{\f36\insrsid4413771\charrsid8023511 allele}{\f36\insrsid9986626\charrsid8023511 , }{\f36\insrsid4413771\charrsid8023511 550delA was present in 3 of 4 alleles, and P82L in one.}{
\f36\insrsid9986626\charrsid8023511 
\par DISCUSSION}{\f36\insrsid5982720 .}{\f36\insrsid154335\charrsid8023511  }{\f36\insrsid9986626\charrsid8023511 Because of h}{\f36\insrsid7820075\charrsid8023511 
igh frequency of healthy 550delA heterozygotes (1 in 133) and relative frequency of healthy heterozygotes for C826A mutation}{\f36\insrsid10637806 , which is}{\f36\insrsid7820075\charrsid8023511  responsible for LGMD2I (1 in 524) in our general population
}{\f36\insrsid5982720 ,}{\f36\insrsid7820075\charrsid8023511  we }{\f36\insrsid10637806 have }{\f36\insrsid7820075\charrsid8023511 decided to }{\f36\insrsid6111759\charrsid8023511 correlate genotype-phenotype }{\f36\insrsid7820075\charrsid8023511 only }{
\f36\insrsid5982720 in}{\f36\insrsid6111759\charrsid8023511  }{\f36\insrsid7820075\charrsid8023511 patients with two known alleles}{\f36\insrsid6111759\charrsid8023511 .}{\f36\insrsid154335\charrsid5982720 
\par }{\f36\insrsid6111759\charrsid8023511 CONCLUSION}{\f36\insrsid5982720 . }{\f36\insrsid12733820\charrsid5982720 To}{\f36\insrsid12733820\charrsid8023511  study natural history of calpainopathy both alleles must be known as well as genetically homogeno
us groups should be follow up according to as simple as possible protocol}{\f36\insrsid5982720 .}{\f36\insrsid6111759 
\par }{\f36\insrsid14827847 
\par }{\f36\insrsid1010584 241 }{\f36\insrsid14827847  rije\'e8}{\f36\insrsid1010584 i}{\f36\insrsid14827847\charrsid8023511 
\par }}