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: Olayinka Raheem, Sini Penttilä, Tiina Suominen, Mika Kaakinen, James Burge, Andrea Haworth, Richa Sud, Stephanie Schorge, Hannu Haapasalo, Satu Sandell, Kalervo Metsikkö, Michael Hanna, Bjarne Udd
• Journal: Neurology (Neurology) Vol. 79 Issue 22 Pg. 2194-200 (Nov 27 2012) ISSN: 1526-632X [Electronic] United States
• PMID: 23152584 (Publication Type: Controlled Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CLC-1 channel
• Chloride Channels

Topics

• Adult
• Aged
• Chloride Channels (genetics, metabolism)
• Female
• Genes, Recessive
• Genetic Testing (methods)
• Humans
• Immunoenzyme Techniques (methods, standards)
• Male
• Middle Aged
• Myotonia Congenita (diagnosis, enzymology, genetics)
• Point Mutation (genetics)
• Reproducibility of Results
• Young Adult