High incidence of 550delA mutation of CAPN3 in LGMD2 patients from Russia

Pogoda, T.V.; Krakhmaleva, I. N.; Lipatova, N.A.; Shakhovskaya, N. I.; Shishkin, S. S.; Limborska, Svetlana A.

doi:10.1002/(sici)1098-1004(200003)15:3<295::aid-humu15>3.0.co;2-8

Cited by 40 publications

(23 citation statements)

References 17 publications

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“…Although LGMD2I is the most common form of all LGMDs in Northern Europe, 1 LGMD2A (MIM#253600) is the most prevalent in many European countries, 2 -10 Turkey, 11,12 Brazil, 13 Japan, 14,15 Russia 16 and Australia, 17 with variable frequencies that differ depending on ethnic clusters and geographic origins. Estimates based on molecular data indicate that LGMD2A frequency ranges from about 10% of LGMD cases in the United States 18,19 to 80% in the Basque country and Russia.…”

Section: Introductionmentioning

confidence: 99%

“…Estimates based on molecular data indicate that LGMD2A frequency ranges from about 10% of LGMD cases in the United States 18,19 to 80% in the Basque country and Russia. 16,20 LGMD2A is caused by mutations in the CAPN3 gene (MIM#114240, mapped to 15q15.1 -q21.1) encoding for a muscle-specific proteolytic enzyme called calpain-3 21 that is involved in the complex process of sarcomere remodeling. 22 Many clinical and molecular studies, carried out on large series of calpainopathy patients, have highlighted the heterogeneous features of the disease at the clinical, molecular and protein levels.…”

Section: Introductionmentioning

confidence: 99%

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How to tackle the diagnosis of limb-girdle muscular dystrophy 2A

et al. 2008

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Limb-girdle muscular dystrophy (LGMD) 2A (calpainopathy) is the most frequent form of LGMD in many European countries. The increasing demand for a molecular diagnosis makes the identification of strategies to improve gene mutation detection crucial. We conducted both a quantitative analysis of calpain-3 protein in 519 muscles from patients with unclassified LGMD, unclassified myopathy and hyperCKemia, and a functional assay of calpain-3 autolytic activity in 108 cases with LGMD and normal protein quantity. Subsequently, screening of CAPN3 gene mutations was performed using allele-specific tests and simplified SSCP analysis. We diagnosed a total of 94 LGMD2A patients, carrying 66 different mutations (six are newly identified). The probability of diagnosing calpainopathy was very high in patients showing either a quantitative (80%) or a functional calpain-3 protein defect (88%). Our data show a high predictive value for reduced-absent calpain-3 or lost autolytic activity. These biochemical assays are powerful tools for otherwise laborious genetic screening of cases with a high probability of being primary calpainopathy. Our multistep diagnostic approach is rational and highly effective. This strategy has improved the detection rate of the disease and our extension of screening to presymptomatic phenotypes (hyperCKemia) has allowed us to obtain early diagnoses, which has important consequences for patient care and genetic counseling.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

How to tackle the diagnosis of limb-girdle muscular dystrophy 2A

et al. 2008

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“…All these mutations are distributed along the entire length of the CAPN3 gene, and small hot spot regions are present in exon 11 and exon 21. Some mutations, such as 550delA, have been found more frequently in some populations (e.g., Russia [24], Croatia [9] and Turkey [31]), but most of them represent private variants. The first extensive CAPN3 mutation study was based on the analysis of 181 families from 19 countries and reports the identification of 97 pathogenic mutations [28].…”

Section: Introductionmentioning

confidence: 99%

Calpain-3 mutations in Turkey

et al. 2006

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Autosomal recessive limb-girdle muscular dystrophies (LGMD2s) are a clinically and genetically heterogeneous group of disorders, characterized by progressive involvement of the proximal limb girdle muscles; the group includes at least 10 different genetic entities. The calpainopathies (LGMD2A), a subgroup of LGMD2s, are estimated to be the most common forms of LGMD2 in all populations so far investigated. LGMD2A is usually characterized by symmetrical and selective atrophy of pelvic, scapular and trunk muscles and a moderate to gross elevation of serum CK. However, the course is highly variable. It is caused by mutations in the CAPN3 gene, which encodes for the calpain-3 protein. Until now, 161 pathogenic mutations have been found in the CAPN3 gene. In the present study, through screening of 93 unrelated LGMD2 families, we identified 29 families with LGMD2A, 21 (22.6%) of which were identified as having CAPN3 gene mutations. We detected six novel (p.K211N, p.D230G, p.Y322H, p.R698S, p.Q738X, c.2257delGinsAA) and nine previously reported mutations (c.550delA, c.19_23del, c.1746-20C>G, p.R49H, p.R490Q, p.Y336N, p.A702V, p.Y537X, p.R541Q) in the CAPN3 gene. There may be a wide variety of mutations, but clustering of specific mutations (c.550delA: 40%, p.R490Q: 10%) could be used in the diagnostic scheme in Turkey.

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“…Так, мутация c. 550delA наиболее распространена в Европейских странах, в том числе и в России [20,[22][23][24] (табл. 1), что, веро-ятно, обусловлено эффектом основателя.…”

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Inherited progressive limb-girdle muscular dystrophy type 2A (calpainopathy): a review of literature

Grishina¹,

Супонева²,

Шведков³

et al. 2015

Neuromuscular Diseases

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1'2015 Нервно-мышечные Б О Л Е З Н И Лекции и обзоры 25Конечностно-поясные мышечные дистрофии (КПМД) -многочисленная гетерогенная группа наслед-ственных прогрессирующих мышечных дистрофий с раз-ными типами наследования и сроками манифестации, для которых характерны преимущественное вовлечение мышц тазового и плечевого поясов, высокая концентра-ция сывороточной креатининфосфокиназы (КФК) и первично-мышечный уровень поражения по данным электромиографического (ЭМГ) исследования.В настоящий момент выделено 30 генетически детерминированных КПМД -7 с аутосомно-доми-нантным типом наследования (КПМД1), диагностиру-емые редко, до 10 % от всех случаев КПМД, и 23 -с аутосомно-рецессивным (КПМД2), выявляемые значительно чаще, до 1 случая на 15 000-42 700 населе-ния в зависимости от географического региона [1,2].Кальпаинопатия (КПМД2А) является наиболее распространенной формой аутосомно-рецессивных прогрессирующих КПМД. Анализ частоты встречае-мости данной патологии, основанный на результатах молекулярно-генетических исследований, показал, что кальпаинопатия среди всех случаев КПМД диаг-ностируется в 12 % в США и Дании [3,4]

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High incidence of 550delA mutation of CAPN3 in LGMD2 patients from Russia

Cited by 40 publications

References 17 publications

How to tackle the diagnosis of limb-girdle muscular dystrophy 2A

How to tackle the diagnosis of limb-girdle muscular dystrophy 2A

Calpain-3 mutations in Turkey

Inherited progressive limb-girdle muscular dystrophy type 2A (calpainopathy): a review of literature

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