title: Protein and genetic diagnosis of limb girdle muscular dystrophy type 2A: The yield and the pitfalls.
abstract: Limb girdle muscular dystrophy type 2A (LGMD2A) is the most frequent form of LGMD worldwide. Comprehensive clinical assessment and laboratory testing is essential for diagnosis of LGMD2A. Muscle immunoblot analysis of calpain-3 is the most useful tool to direct genetic testing, as detection of calpain-3 deficiency has high diagnostic value. However, calpain-3 immunoblot testing lacks sensitivity in about 30% of cases due to gene mutations that inactivate the enzyme. The best diagnostic strategy should be determined on a case-by-case basis, depending on which tissues are available, and which molecular and/or genetic methods are adopted. In this work we survey the current knowledge, advantages, limitations, and pitfalls of protein testing and mutation detection in LGMD2A and provide an update of genetic epidemiology.
authors.affiliation: Department of Neurosciences, Biomedical Campus "Pietro d'Abano," via Giuseppe Orus 2B, 35129, Padova, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Fanin
authors.affiliation: Fondazione Ospedale San Camillo IRCCS, Venice, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Angelini
mesh_terms: D000818:Animals; D002154:Calpain / Q000172:deficiency / Q000235:genetics; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D009124:Muscle Proteins / Q000172:deficiency* / Q000235:genetics*; D049288:Muscular Dystrophies, Limb-Girdle / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation / Q000235:genetics
chemical_list: D009124:Muscle Proteins; C105884:CAPN3 protein, human; D002154:Calpain
keywords: LGMD2A; calpain-3; calpainopathy; genetic diagnosis; immunoblot analysis; limb girdle muscular dystrophy; mutation detection; protein testing