Figure 3. Reduced size and amount of titin in patients with centronuclear myopathy carrying TTN mutations.

Gel electrophoresis of patient muscle proteins with control human soleus (HS) and cardiac (HC) muscle proteins. Both controls were run on the same gel to observe the various known titin isoforms present in the 2 muscle types that have been sequenced and therefore can serve as high-molecular-weight markers. Their molecular masses (in MDa) are shown in parentheses. The predominant titin isoforms expressed in skeletal (N2A, 3.8 MDa) and cardiac (N2BA, ∼3.5 MDa and N2B, 3.0 MDa) muscles are marked. The titin degradation product T2 (2.1 MDa) and nebulin (0.77 MDa) are shown as well. The known molecular masses were used to estimate the molecular masses of titin species present in the patients. Patient 1044-1: ∼3.8, ∼2.7, and ∼2.1 MDa; patient 1093-1: ∼3.5 and 2.3 MDa. Myosin heavy chain (MHC) was used as a loading control. Pt = patient.