OMIA:001464-9913 : Pseudomyotonia, congenital in Bos taurus (taurine cattle)
In other species: dog
Categories: Muscle phene
Links to MONDO diseases:
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2008
Species-specific name: Congenital pseudomyotonia
Species-specific symbol: PMT
History: This disorder was first described in cattle by Testoni et al. (2008).
Molecular basis: Recognising the close resemblance of this disorder in Chianina cattle to Brody disease in humans, Drögemüller et al. (2008) illustrated the power of the candidate-gene approach by showing that this disorder in Chianina cattle is due to a missense mutation in the bovine version of the "Brody gene" - ATP2A1.
Interestingly, another mutation in this same gene causes a far more severe set of clinical signs: congenital muscular dystonia 1 (OMIA 001450-9913).
The situation has been complicated somewhat with the discovery by Grunberg et al. (2010) of a Dutch Improved Red and White cross-bred calf with clinical signs of PMT yet with the same mutation as seen in the Belgian Blue with congenital muscular dystonia 1 (OMIA 001450-9913). They raise the very real (and not unexpected) possibility that the same mutation can have different effects in different breeds. Dorotea et al. (2015) shed some light on this enigma.
Murgiano et al. (2012) identified the causal mutation in Romagnola cattle as two separate missense base substitutions in "exon 8 (c.[632 G>T; 857 G>T])" resulting in two amino-acid substitutions "(p.[(Gly211Val; Gly284Val)])" at highly conserved residues. Interestingly, only one of the four affected calves in this study was homozygous for the newly-identified double mutation; the other three affected calves were compound heterozygotes for the double mutation and the "exon 6 variant c.491 G>A(p. Arg146Gly)" reported by Drögemüller et al. (2008) in Chianina cattle.
Akyürek et al. (2022) "analyzed the consequences of G211V and G286V mutations [reported previously in Romagnola cattle]. Results support that the reduced amount of SERCA1 is a consequence of the G211V mutation, the G286V mutation almost being benign and the ubiquitin–proteasome system (UPS) being involved."
Chianina (Cattle) (VBO_0000178),
Maas-Rijn-Ijssel (Cattle) (VBO_0000285),
Marchigiana (Cattle) (VBO_0000291),
Romagnola (Cattle) (VBO_0000360).
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|
|ATP2A1||ATPase, Ca++ transporting, cardiac muscle, fast twitch 1||Bos taurus||25||NC_037352.1 (25946606..25929252)||ATP2A1||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|
|219||Romagnola (Cattle)||Pseudomyotonia, congenital||ATP2A1||missense||Naturally occurring variant||ARS-UCD1.2||25||g.25939141C>A||c.857G>T||p.(G286V)||This variant was identified as part of a haplotype with the G211V variant in Romagnola cattle. Akyürek et al. (2022; PMID: 36293223) suggest that the G286V variant is likely to be benign and that the G211V is likely to be causal.||rs3423529256||2012||23046865||Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool; Breed information kindly provided or confirmed by Matt McClure and Jennifer McClure from "Understanding Genetics and Complete Genetic Disease and Trait Definition (Expanded 2016 Edition)" (https://www.icbf.com/wp/?page_id=2170)|
|218||Romagnola (Cattle)||Pseudomyotonia, congenital||ATP2A1||missense||Naturally occurring variant||ARS-UCD1.2||25||g.25939366C>A||c.632G>T||p.(G211V)||2012||23046865||Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool; Breed information kindly provided or confirmed by Matt McClure and Jennifer McClure from "Understanding Genetics and Complete Genetic Disease and Trait Definition (Expanded 2016 Edition)" (https://www.icbf.com/wp/?page_id=2170)|
|205||Chianina (Cattle) Marchigiana (Cattle) Romagnola (Cattle)||Pseudomyotonia, congenital||ATP2A1||missense||Naturally occurring variant||ARS-UCD1.2||25||g.25940510C>T||c.491G>A||p.(R164H)||Variant initially identified in Chianina cattle and later reported in additional breeds: PMID: 35717834||rs3423529241||2008||18786632||Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool; Breed information kindly provided or confirmed by Matt McClure and Jennifer McClure from "Understanding Genetics and Complete Genetic Disease and Trait Definition (Expanded 2016 Edition)" (https://www.icbf.com/wp/?page_id=2170)|
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||Akyürek, E.E., Busato, F., Murgiano, L., Bianchini, E., Carotti, M., Sandonà, D., Drögemüller, C., Gentile, A., Sacchetto, R. :|
|Differential analysis of Gly211Val and Gly286Val mutations affecting sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA1) in congenital pseudomyotonia Romagnola cattle. Int J Mol Sci 23:, 2022. Pubmed reference: 36293223 . DOI: 10.3390/ijms232012364.|
|Jacinto, J.G.P., Sbarra, F., Quaglia, A., Gentile, A., Drögemüller, C. :|
|Short communication: Prevalence of deleterious variants causing recessive disorders in Italian Chianina, Marchigiana and Romagnola cattle. Animal 16:100569, 2022. Pubmed reference: 35717834 . DOI: 10.1016/j.animal.2022.100569.|
|2021||Caivio-Nasner, S., López-Herrera, A., González-Herrera, L.G., Rincón, J.C. :|
|Frequency of genotypic markers for genetic disorders, colour, polledness, and major genes in Blanco Orejinegro cattle. Trop Anim Health Prod 53:546, 2021. Pubmed reference: 34779908 . DOI: 10.1007/s11250-021-02990-y.|
|2015||Dorotea, T., Grünberg, W., Murgiano, L., Plattet, P., Drögemüller, C., Mascarello, F., Sacchetto, R. :|
|Fast-twitch skeletal muscle fiber adaptation to SERCA1 deficiency in a Dutch Improved Red and White calf pseudomyotonia case. Neuromuscul Disord 25:888-97, 2015. Pubmed reference: 26482047 . DOI: 10.1016/j.nmd.2015.08.010.|
|2013||Murgiano, L., Testoni, S., Drögemüller, C., Bolcato, M., Gentile, A. :|
|Frequency of bovine congenital pseudomyotonia carriers in selected Italian Chianina sires. Vet J 195:238-40, 2013. Pubmed reference: 22627047 . DOI: 10.1016/j.tvjl.2012.04.021.|
|2012||Murgiano, L., Sacchetto, R., Testoni, S., Dorotea, T., Mascarello, F., Liguori, R., Gentile, A., Drogemuller, C. :|
|Pseudomyotonia in Romagnola cattle caused by novel ATP2A1 mutations. BMC Vet Res 8:186, 2012. Pubmed reference: 23046865 . DOI: 10.1186/1746-6148-8-186.|
|2010||Grünberg, W., Sacchetto, R., Wijnberg, I., Neijenhuis, K., Mascarello, F., Damiani, E., Drögemüller, C. :|
|Pseudomyotonia, a muscle function disorder associated with an inherited ATP2A1 (SERCA1) defect in a Dutch Improved Red and White cross-breed calf. Neuromuscul Disord 20:467-70, 2010. Pubmed reference: 20547455 . DOI: 10.1016/j.nmd.2010.04.010.|
|2009||Sacchetto, R., Testoni, S., Gentile, A., Damiani, E., Rossi, M., Liguori, R., Drögemüller, C., Mascarello, F. :|
|A defective SERCA1 protein is responsible for congenital pseudomyotonia in Chianina cattle. Am J Pathol 174:565-73, 2009. Pubmed reference: 19116366 . DOI: 10.2353/ajpath.2009.080659.|
|2008||Drögemüller, C., Drögemüller, M., Leeb, T., Mascarello, F., Testoni, S., Rossi, M., Gentile, A., Damiani, E., Sacchetto, R. :|
|Identification of a missense mutation in the bovine ATP2A1 gene in congenital pseudomyotonia of Chianina cattle: an animal model of human Brody disease. Genomics 92:474-7, 2008. Pubmed reference: 18786632 . DOI: 10.1016/j.ygeno.2008.07.014.|
|Testoni, S., Boni, P., Gentile, A. :|
|Congenital pseudomyotonia in Chianina cattle. Vet Rec 163:252, 2008. Pubmed reference: 18723868 .|
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