title: New immunohistochemical method for improved myotonia and chloride channel mutation diagnostics.
abstract: OBJECTIVE
  The objective of this study was to validate the immunohistochemical assay for the diagnosis of nondystrophic myotonia and to provide full clarification of clinical disease to patients in whom basic genetic testing has failed to do so.
  
  
  METHODS
  An immunohistochemical assay of sarcolemmal chloride channel abundance using 2 different ClC1-specific antibodies.
  
  
  RESULTS
  This method led to the identification of new mutations, to the reclassification of W118G in CLCN1 as a moderately pathogenic mutation, and to confirmation of recessive (Becker) myotonia congenita in cases when only one recessive CLCN1 mutation had been identified by genetic testing.
  
  
  CONCLUSIONS
  We have developed a robust immunohistochemical assay that can detect loss of sarcolemmal ClC-1 protein on muscle sections. This in combination with gene sequencing is a powerful approach to achieving a final diagnosis of nondystrophic myotonia.
authors.affiliation: Neuromuscular Research Unit, University of Tampere and Tampere University Hospital, Tampere, Finland. olayinka.raheem@uta.fi
authors.forename: Olayinka
authors.initials: O
authors.lastname: Raheem
authors.forename: Sini
authors.initials: S
authors.lastname: Penttilä
authors.forename: Tiina
authors.initials: T
authors.lastname: Suominen
authors.forename: Mika
authors.initials: M
authors.lastname: Kaakinen
authors.forename: James
authors.initials: J
authors.lastname: Burge
authors.forename: Andrea
authors.initials: A
authors.lastname: Haworth
authors.forename: Richa
authors.initials: R
authors.lastname: Sud
authors.forename: Stephanie
authors.initials: S
authors.lastname: Schorge
authors.forename: Hannu
authors.initials: H
authors.lastname: Haapasalo
authors.forename: Satu
authors.initials: S
authors.lastname: Sandell
authors.forename: Kalervo
authors.initials: K
authors.lastname: Metsikkö
authors.forename: Michael
authors.initials: M
authors.lastname: Hanna
authors.forename: Bjarne
authors.initials: B
authors.lastname: Udd
mesh_terms: D000328:Adult; D000368:Aged; D018118:Chloride Channels / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005808:Genes, Recessive; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D007124:Immunoenzyme Techniques / Q000379:methods* / Q000592:standards*; D008297:Male; D008875:Middle Aged; D009224:Myotonia Congenita / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics; D015203:Reproducibility of Results; D055815:Young Adult
chemical_list: C086321:CLC-1 channel; D018118:Chloride Channels