A missense mutation in the skeletal muscle chloride channel 1 (CLCN1) as candidate causal mutation for congenital myotonia in a New Forest pony

Wijnberg, Inge D.; Owczarek-Lipska, Marta; Sacchetto, Roberta; Mascarello, Francesco; Pascoli, Francesco; Grünberg, Walter; van der Kolk, Johannes H.; Drögemüller, Cord

doi:10.1016/j.nmd.2011.10.001

« Previous Next »Neuromuscular Disorders
Volume 22, Issue 4 , Pages 361-367, April 2012

A missense mutation in the skeletal muscle chloride channel 1 (CLCN1) as candidate causal mutation for congenital myotonia in a New Forest pony

Inge D. Wijnberg
- Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
- Corresponding author. Address: Department Equine Sciences, Utrecht University, Yalelaan 114-116, 3584 CM Utrecht, The Netherlands. Tel.: +31 30 253 1350; fax: +31 30 2537970.
Marta Owczarek-Lipska
- Institute of Genetics, Vetsuisse Faculty, University of Berne, Switzerland
Roberta Sacchetto
- Department of Experimental Veterinary Sciences, University of Padova, Padova, Italy
Francesco Mascarello
- Department of Experimental Veterinary Sciences, University of Padova, Padova, Italy
Francesco Pascoli
- Department of Experimental Veterinary Sciences, University of Padova, Padova, Italy
Walter Grünberg
- Department of Farm Animal Health, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
Johannes H. van der Kolk
- Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
Cord Drögemüller
- Institute of Genetics, Vetsuisse Faculty, University of Berne, Switzerland

Received 3 June 2011; received in revised form 26 September 2011; accepted 3 October 2011. published online 26 December 2011.

Abstract

A 7-month-old New Forest foal presented for episodes of recumbency and stiffness with myotonic discharges on electromyography. The observed phenotype resembled congenital myotonia caused by CLCN1 mutations in goats and humans. Mutation of the CLCN1 gene was considered as possible cause and mutation analysis was performed. The affected foal was homozygous for a missense mutation (c.1775A>C, p.D592A) located in a well conserved domain of the CLCN1 gene. The mutation showed a recessive mode of inheritance within the reported pony family. Therefore, this CLCN1 polymorphism is considered to be a possible cause of congenital myotonia.

Keywords: Muscle spasm, Myotonic discharges, Electromyography, Becker, Thomsen, CLCN1, Horse