OMIA 001464-9913 : Pseudomyotonia, congenital in Bos taurus

Possibly relevant human trait(s) and/or gene(s) (MIM number): 601003

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, Drogemuller 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 Drogemuller et al. (2008) in Chianina cattle.

Breeds: Chianina, Red and White Dutch, Romagnola.

Associated gene:

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 (25946618..25929251) ATP2A1 Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective.

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Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Romagnola Pseudomyotonia, congenital ATP2A1 missense UMD3.1 25 g.26197204G>T c.857G>T p.G286V 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)
Romagnola Pseudomyotonia, congenital ATP2A1 missense UMD3.1 25 g.26197429G>T 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)
Chianina Pseudomyotonia, congenital ATP2A1 missense UMD3.1 25 g.26198573G>A c.491G > A p.R164H 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)

References


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.
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.

Edit History


  • Created by Frank Nicholas on 15 Jul 2010
  • Changed by Frank Nicholas on 07 Oct 2011
  • Changed by Frank Nicholas on 09 Dec 2011
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  • Changed by Frank Nicholas on 16 Aug 2013
  • Changed by Frank Nicholas on 31 Jul 2017