Table 3.
Primary and secondary protein abnormalities in muscular dystrophies
| Disease | Gene(s) | Primary protein defect | Secondary changes |
|---|---|---|---|
| DMD | DMD | Dystrophin absent or very reduced with all antibodies | Utrophin overall upregulated Sarcoglycans reduced/absent Dystroglycan reduced/absent nNOS absent |
| BMD | DMD | Dystrophin reduced in size or amount or absent with at least one antibody | Utrophin overall upregulated Sarcoglycans reduced/absent Dystroglycan reduced/absent nNOS may be absent |
| DMD/BMD carriers | DMD | Dystrophin patchy, mosaic pattern with at least one antibody | In fibres without dystrophin Utrophin upregulated Sarcoglycans reduced/absent Dystroglycan reduced/absent nNOS may be absent |
| EDMD1 | EMD | Emerin absent | |
| LGMD1A MFM | MYOT | Myotilin cytoplasmic aggregates | Desmin, αB-crystallin, VCP cytoplasmic aggregates |
| LGMD1B EDMD2 EDMD3 | LMNA | Lamin A/C normally expressed | |
| LGMD1C rippling muscle disease hyperCKemia | CAV3 | Caveolin-3 absent/reduced | Dysferlin reduced at the sarcolemma |
| LGMD2A | CAPN3 | Calpain 3 bands may be variably reduced on immunoblot, Iabelling may be absent or reduced on sections | Dysferlin reduced at the sarcolemma |
| LGMD2B Miyoshi myopathy | DYSF | Dysferlin absent or very reduced | Caveolin-3 reduced at the sarcolemma, calpain 3 bands may be reduced |
| LGMD2C-F |
SGCG SGCA SGCB SGCD |
Sarcoglycans variably reduced/absent | β-Dystroglycan may be reduced Dystrophin may be reduced nNOS may be absent |
| LGMD2G | TCAP | Telethonin absent | |
| LGMD2I, K, M-O, DG-pathies | FKRP POMT1 FKTN POMT2 POMGnT1 LARGE | Not applicable | Glycosylated α-dystroglycan very reduced/patchy β-dystroglycan may be reduced Laminin α2 may be reduced |
| MDC1A | LAMA2 | Laminin α2 completely or partially absent | Laminin α5 overall upregulated α-dystroglycan may be reduced |
| UCMD and Bethlem myopathy | COL6A1 COL6A2 COL6A3 | Collagen VI very reduced in UCMD, usually normally expressed in BMD | |
| MD with lipodystrophy | PTRF | PTRF-cavin absent/very reduced | Caveolin-3 reduced at the sarcolemma |
| MFM | DES | Desmin cytoplasmic aggregates | Myotilin, αB-crystallin, VCP cytoplasmic aggregates |
| MFM | CRYAB | αB-Crystallin cytoplasmic aggregates | Myotilin, desmin, VCP cytoplasmic aggregates |
| IBMPFD | VCP | VCP cytoplasmic aggregates | Myotilin, desmin, αB-crystallin cytoplasmic aggregates |
BMD = Becker muscular dystrophy; CK = creatine kinase; DG-pathies = dystroglycanopathies; DMD = Duchenne muscular dystrophy; EDMD = Emery-Dreifuss muscular dystrophy; IBMPFD = inclusion body myopathy with Paget's disease and frontotemporal dementia; LGMD = limb girdle muscular dystrophy; MD = muscular dystrophy; MDC = congenital muscular dystrophy; MFM = myofibrillar myopathy; nNOS = neuronal nitric oxide synthase; PTRF = polymerase I and transcript release factor; UCMD = Ulrich congenital muscular dystrophy; VCP = valosin-containing protein.