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

Marina Fanin, Anna Chiara Nascimbeni, Elisabetta Tasca, Corrado Angelini

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)598-603
Number of pages6
JournalEuropean Journal of Human Genetics
Volume17
Issue number5
DOIs
Publication statusPublished - 2009

Fingerprint

Calpain
Limb-Girdle Muscular Dystrophies
Mutation
Single-Stranded Conformational Polymorphism
Proteins
Genetic Counseling
Genetic Testing
Muscular Diseases
Genes
Early Diagnosis
Patient Care
Alleles
Limb-girdle muscular dystrophy type 2A
Phenotype
Muscles

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

How to tackle the diagnosis of limb-girdle muscular dystrophy 2A. / Fanin, Marina; Nascimbeni, Anna Chiara; Tasca, Elisabetta; Angelini, Corrado.

In: European Journal of Human Genetics, Vol. 17, No. 5, 2009, p. 598-603.

Research output: Contribution to journalArticle

Fanin, M, Nascimbeni, AC, Tasca, E & Angelini, C 2009, 'How to tackle the diagnosis of limb-girdle muscular dystrophy 2A', European Journal of Human Genetics, vol. 17, no. 5, pp. 598-603. https://doi.org/10.1038/ejhg.2008.193
Fanin, Marina ; Nascimbeni, Anna Chiara ; Tasca, Elisabetta ; Angelini, Corrado. / How to tackle the diagnosis of limb-girdle muscular dystrophy 2A. In: European Journal of Human Genetics. 2009 ; Vol. 17, No. 5. pp. 598-603.
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