title: Leukocyte CTG repeat length correlates with severity of myotonia in myotonic dystrophy type 1.
abstract: OBJECTIVE
  To quantitate hand muscle myotonia and to assess the relationship between CTG repeat length and myotonia in myotonic dystrophy type 1 (DM1).
  
  
  METHODS
  First dorsal interosseous twitch and tetanic contractions evoked by single and 10-Hz ulnar nerve stimulation were recorded with a force transducer in 15 patients with genetically confirmed DM1 and 15 control subjects. An automated computer program analyzed three single and three tetanic recordings per subject on 2 successive days by placing cursors along the declining (relaxation) phase of the force recordings at 90, 50, and 5% of peak force (PF) and calculating relaxation times (RT) between these points.
  
  
  RESULTS
  Tetanic and twitch RT was longer and PF lower in patients than subjects. RT (90 to 5%) was above the normal mean + 2.5 SD in 13 tetanic (87%) and 11 (73%) twitch patient recordings. In DM1, prolongation of RT was due mainly to delay in the terminal (50 to 5%), rather than the initial (90 to 50%) phase of relaxation, and was much greater in tetanic than single-twitch recordings. Mean test-retest variability was 19% for tetanic RT and 16% for tetanic PF. In DM1, both tetanic and twitch RT were positively correlated with leukocyte CTG repeat length.
  
  
  CONCLUSIONS
  In DM1, myotonia of intrinsic hand muscles can be quantitated reliably by automated analysis of tetanic and twitch RT, targeting, in particular, the terminal phase of muscle relaxation after tetanic stimulation. Severity of hand muscle myotonia depends on CTG repeat length consistent with a "triplet repeat dosage" effect on chloride channel mRNA splicing and function.
authors.affiliation: Department of Neurology, University of Rochester, NY, USA. eric_logigian@urmc.rochester.edu
authors.forename: E L
authors.initials: EL
authors.lastname: Logigian
authors.forename: R T
authors.initials: RT
authors.lastname: Moxley
authors.forename: C L
authors.initials: CL
authors.lastname: Blood
authors.forename: C A
authors.initials: CA
authors.lastname: Barbieri
authors.forename: W B
authors.initials: WB
authors.lastname: Martens
authors.forename: A W
authors.initials: AW
authors.lastname: Wiegner
authors.forename: C A
authors.initials: CA
authors.lastname: Thornton
authors.forename: R T
authors.initials: RT
authors.lastname: Moxley
mesh_terms: D000328:Adult; D004558:Electric Stimulation; D004568:Electrodiagnosis / Q000295:instrumentation / Q000379:methods*; D005240:Feasibility Studies; D005260:Female; D006225:Hand / Q000503:physiopathology; D006801:Humans; D007962:Leukocytes / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000235:genetics; D018482:Muscle, Skeletal / Q000503:physiopathology; D009223:Myotonic Dystrophy / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D065636:Myotonin-Protein Kinase; D011237:Predictive Value of Tests; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012016:Reference Values; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*; D014459:Ulnar Nerve / Q000503:physiopathology
chemical_list: C585517:DMPK protein, human; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases