title: Sarcoglycanopathies: can muscle immunoanalysis predict the genotype?
abstract: Muscle immunoanalysis of the sarcoglycan complex is an important part of the diagnostic evaluation of muscle biopsies in patients with autosomal recessive limb-girdle muscular dystrophy. Reduced or absent sarcolemmal expression of one or all of the four sarcoglycans (alpha-, beta-, gamma-, delta-sarcoglycan) can be found in patients with limb-girdle muscular dystrophy 2C-F (LGMD2C-F) and also in patients with Duchenne and Becker muscular dystrophy (DMD/BMD). It has previously been suggested that different patterns of sarcoglycan expression could predict the primary genetic defect, and that genetic analysis could be directed by these patterns. In this first UK study we studied 24 genetically characterized patients with sarcoglycan deficient LGMD, in 22 of whom muscle immunoanalysis data were available. Thirteen patients showed alpha-sarcoglycan deficient LGMD2D, 7 patients beta-sarcoglycan deficient LGMD2E, 3 patients gamma-sarcoglycan deficient LGDM2C, and one patient delta-sarcoglycan deficient LGMD2F. Muscle biopsies were analysed in one centre without knowledge of the established genetic diagnosis. Our results demonstrated that residual sarcoglycan expression is highly variable and does not enable an accurate prediction of the genotype. Considering previous reports of sarcoglycanopathy patients with an isolated loss of one sarcoglycan we recommend to use antibodies against all four sarcoglycans for immunoanalysis of skeletal muscle sections. A concomitant reduction of dystrophin and beta-dystroglycan was observed more frequently than previously reported and illustrates the important differential diagnosis of DMD and BMD for sarcoglycan deficient LGMD.
authors.affiliation: Institute of Human Genetics, University of Newcastle upon Tyne, International Centre for Life, Central Parkway, NE1 3BZ Newcastle-upon-Tyne, UK.
authors.forename: Lars
authors.initials: L
authors.lastname: Klinge
authors.forename: Gabriele
authors.initials: G
authors.lastname: Dekomien
authors.forename: Ahmed
authors.initials: A
authors.lastname: Aboumousa
authors.forename: Richard
authors.initials: R
authors.lastname: Charlton
authors.forename: Jörg T
authors.initials: JT
authors.lastname: Epplen
authors.forename: Rita
authors.initials: R
authors.lastname: Barresi
authors.forename: Kate
authors.initials: K
authors.lastname: Bushby
authors.forename: Volker
authors.initials: V
authors.lastname: Straub
mesh_terms: D000293:Adolescent; D015153:Blotting, Western; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005808:Genes, Recessive; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology*; D049288:Muscular Dystrophies, Limb-Girdle / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D010641:Phenotype; D049031:Sarcoglycans / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: C526571:SGCA protein, human; C483098:SGCB protein, human; C526570:SGCD protein, human; C526573:SGCG protein, human; D049031:Sarcoglycans