In other species: dog

Categories: Muscle phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 601003 (trait) , 108730 (gene)

Links to MONDO diseases:

• MONDO:0010977: Brody myopathy

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 Grünberg et al. (2010) of a Dutch Improved Red and White cross-bred calf with clinical signs of PMT yet with the same mutation (OMIAvariantID:188; p.(R559C)) 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."

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

Breeds: 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

Associated gene: