Childhood spinal muscular atrophy induces alterations in contractile and regulatory protein isoform expressions

Neuropathol Appl Neurobiol. 2008 Dec;34(6):659-70. doi: 10.1111/j.1365-2990.2008.00950.x. Epub 2008 Mar 20.


Aims: Although modifications of the survival motor neurone gene are responsible for most spinal muscular atrophy (SMA) cases, the molecular pathophysiology and the muscular target proteins involved are still unknown. The aim of this study was to compare the expression of contractile and regulatory protein isoforms in quadriceps muscles from SMA children with age-matched control quadriceps.

Methods: The isoform patterns of myosin heavy chains (MHC), troponin subunits (T, C and I) and tropomyosin were determined by immunoblotting, reverse transcription-polymerase chain reaction and mass spectrometry analyses. Depending on the disease severity, their expression levels were followed in specific variants of SMA populations (types I, II and III), with comparison with age-matched control muscles.

Results: The isoform transitions in SMA muscles were different from the fast-to-faster transitions occurring in normal muscles from children aged 1 month to 5 years old. Moreover, the expression of the neonatal MHC isoform was not repressed in SMA muscles.

Conclusions: The presence of the neonatal MHC isoform in SMA muscles indicates an alteration of the phenotype in these diseased muscles. It is strongly suggested that MHC and troponin T proteins may be good markers for the SMA pathology.

MeSH terms

  • Amino Acid Sequence
  • Analysis of Variance
  • Biopsy
  • Child, Preschool
  • Contractile Proteins / genetics
  • Contractile Proteins / metabolism*
  • Gene Expression
  • Humans
  • Immunoblotting
  • Infant
  • Mass Spectrometry
  • Myosin Heavy Chains / genetics
  • Myosin Heavy Chains / metabolism
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Quadriceps Muscle / metabolism*
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spinal Muscular Atrophies of Childhood / genetics
  • Spinal Muscular Atrophies of Childhood / metabolism*
  • Tropomyosin / genetics
  • Tropomyosin / metabolism
  • Troponin C / genetics
  • Troponin C / metabolism
  • Troponin I / genetics
  • Troponin I / metabolism
  • Troponin T / genetics
  • Troponin T / metabolism


  • Contractile Proteins
  • Protein Isoforms
  • RNA, Messenger
  • Tropomyosin
  • Troponin C
  • Troponin I
  • Troponin T
  • Myosin Heavy Chains