OMIA:000698-9796 : Myotonia in Equus caballus (horse)
Categories: Muscle phene
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2012
Cross-species summary: Myotonia congenita
Species-specific description: As summarised by Valberg (2014), "Myotonic muscle disorders share the feature of delayed relaxation of muscle after mechanical stimulation or voluntary contraction due to abnormal muscle membrane conduction. Horses have three known forms of myotonia: myotonia congenita, myotonia dystrophica, and hyperkalemic periodic paralysis (HyPP)". This OMIA entry deals with Myotonia congentia. (FN thanks Izabela De Assis Rocha, who provided the basis of this contribution, working under the supervision of Professor Ernie Bailey; 15 April 2020)
Molecular basis: A gene defect in CLCN1 was then known to cause similar phenotypes in humans (see OMIM links above) and in goats (OMIA 000698-9925 and in dogs (OMIA 000698-9615), which led Wijnberg et al (2012) to adopt a comparative candidate gene approach. By sequencing "all exons and several introns of the equine CLCN1 gene [in] . . . DNA samples from the affected foal, its dam, its sire . . . and one unrelated control horse", and testing variants for consistency with autosomal recessive transmission of the disorder, Wijnberg et al. (2014) identified a likely causal variant as a single nucleotide polymorphism at c.1775A>C position (Genbank acc. XM_001915636). The c.1775A>C transversion led to the replacement of an aspartic acid by alanine in codon 592 (Genbank acc. XP_001915671) in the C-terminal cytoplasmatic domain of the skeletal muscle chloride channel 1 protein. This amino acid residue was found to be conserved in seven other species; therefore the described amino acid substitution has a potential impact on the formation of the functional ion channel (Wijnberg et al., 2012). (FN thanks Izabela De Assis Rocha, who provided the basis of this contribution, working under the supervision of Professor Ernie Bailey; 15 April 2020)
Have human generated variants been created, e.g. through genetic engineering and gene editing
Clinical features: From the case report described in a New Forest Pony by Wijnberg et al. (2012), the main clinical signs of myotonia congenita are the "recurrent episodes of recumbency and difficulty to rise due to muscle stiffness". Occasionally, when the horse is stimulated, it "seemed hyperreactive and temporary protrusion of the third eyelid occurred due to retraction of the eye uni- or bilaterally". It is important to note that this case report included only one affected foal. (FN thanks Izabela De Assis Rocha, who provided the basis of this contribution, working under the supervision of Professor Ernie Bailey; 15 April 2020)
Prevalence: The occurrence of this variant in a wider sample of 42 additional New Forest ponies and 56 horses from 13 other breeds was consistent with it being causal of an autosomal recessive disorder in the New Forest breed: from the total 102 horses included in this study, Wijnberg et al (2012) found that the affected foal was the only homozygous C/C for the mutated allele 1775C, whereas its sire, its dam and seven other mares related to the foal were heterozygous A/C. All other horses here homozygous A/A for the wildtype allele 1775A.
New Forest Pony (Horse) (VBO_0001026).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|CLCN1||chloride channel, voltage-sensitive 1||Equus caballus||4||NC_009147.3 (96497829..96527024)||CLCN1||Homologene, Ensembl , NCBI gene|
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|161||New Forest Pony (Horse)||Myotonia||CLCN1||missense||Naturally occurring variant||EquCab3.0||4||g.96518592A>C||c.1775A>C||p.(D592A)||c.1775A>C, Genbank acc. XM_001915636); p.D592A, Genbank acc. XP_001915671 (Wijnberg et al., 2014)||2012||22197188||(FN thanks Izabela De Assis Rocha, who provided genomic location in EquCab3.0 and the Genbank acc IDs, working under the supervision of Professor Ernie Bailey; 15 April 2020) Revised genomic location kindly provided by Cord Drögemüller; 21 May 2021|
Cite this entry
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
|2022||Aleman, M., Scalco, R., Malvick, J., Grahn, R.A., True, A., Bellone, R.R. :|
|Prevalence of genetic mutations in horses with muscle disease from a neuromuscular disease laboratory. J Equine Vet Sci 118:104129, 2022. Pubmed reference: 36150530. DOI: 10.1016/j.jevs.2022.104129.|
|2014||Valberg, S.J. :|
|Myotonic Disorders in Horses MSD (Veterinary) Manual [https://www.msdvetmanual.com/musculoskeletal-system/myopathies-in-horses/myotonic-disorders-in-horses] , 2014.|
|2012||Wijnberg, I.D., Owczarek-Lipska, M., Sacchetto, R., Mascarello, F., Pascoli, F., Grünberg, W., van der Kolk, J.H., Drögemüller, C. :|
|A missense mutation in the skeletal muscle chloride channel 1 (CLCN1) as candidate causal mutation for congenital myotonia in a New Forest pony. Neuromuscul Disord 22:361-7, 2012. Pubmed reference: 22197188. DOI: 10.1016/j.nmd.2011.10.001.|
|1988||Reed, S.M., Hegreberg, G.A., Bayly, W.M., Brown, C.M., Paradis, M.R., Clemmons, R.M. :|
|Progressive myotonia in foals resembling human dystrophia myotonica. Muscle Nerve 11:291-6, 1988. Pubmed reference: 3398875. DOI: 10.1002/mus.880110403.|
|1987||Jamison, J.M., Baird, J.D., Smith-Maxie, L.L., Hulland, T.J. :|
|A congenital form of myotonia with dystrophic changes in a quarterhorse. Equine Vet J 19:353-8, 1987. Pubmed reference: 3622468.|
|McKerrell, R.E. :|
|Myotonia in man and animals: confusing comparisons. Equine Vet J 19:266-7, 1987. Pubmed reference: 3622451.|
|1962||Steinberg, S., Botelho, S. :|
|Myotonia in a horse. Science 137:979-80, 1962. Pubmed reference: 13916691.|
- Created by Frank Nicholas on 16 Jan 2012
- Changed by Frank Nicholas on 17 Aug 2012
- Changed by Frank Nicholas on 15 Apr 2020
- Changed by Imke Tammen2 on 20 Oct 2023