Pseudomyotonia in Romagnola cattle caused by novel ATP2A1mutations

Leonardo Murgiano,Cord Drögemüller,Stefania Testoni,Tiziano Dorotea,Rocco Liguori,Roberta Sacchetto,Arcangelo Gentile,Francesco Mascarello

doi:10.1186/1746-6148-8-186

Abstract

BackgroundBovine congenital pseudomyotonia (PMT) is an impairment of muscle relaxation induced by exercise preventing animals from performing rapid movements. Forms of recessively inherited PMT have been described in different cattle breeds caused by two independent mutations in ATP2A1 encoding a skeletal-muscle Ca2+-ATPase (SERCA1). We observed symptoms of congenital PMT in four related Romagnola beef cattle from Italy and evaluated SERCA1 activity and scanned ATP2A1 for possible causative mutations.ResultsWe obtained four PMT affected Romagnola cattle and noted striking clinical similarities to the previously described PMT cases in other cattle breeds. The affected animals had a reduced SERCA1 activity in the sarcoplasmic reticulum. A single affected animal was homozygous for a novel complex variant in ATP2A1 exon 8 (c.[632 G>T; 857 G>T]). Three out of four cases were compound heterozygous for the newly identified exon 8 variant and the exon 6 variant c.491 G>A(p. Arg146Gly), which has previously been shown to cause PMT in Chianina cattle. Pedigree analysis showed that the exon 8 double mutation event dates back to at least 1978. Both nucleotide substitutions are predicted to alter the SERCA1 amino acid sequence (p.[(Gly211Val; Gly284Val)]), affect highly conserved residues, in particular the actuator domain of SERCA1.ConclusionClinical, biochemical and DNA analyses confirmed the initial hypothesis. We provide functional and genetic evidence that one novel and one previously described ATP2A1 mutation lead to a reduced SERCA1 activity in skeletal muscles and pseudomyotonia in affected Romagnola cattle. Selection against these mutations can now be used to eliminate the mutant alleles from the Romagnola breed.

Highlights

Bovine congenital pseudomyotonia (PMT) is an impairment of muscle relaxation induced by exercise that prevents animals from performing rapid movements
In Chianina cattle, we have described PMT as autosomal recessive inherited disorder caused by a missense mutation
The clinical picture strongly resembled the signs of PMT in Chianina cattle [1]

Summary

Introduction

Bovine congenital pseudomyotonia (PMT) is an impairment of muscle relaxation induced by exercise preventing animals from performing rapid movements. Bovine congenital pseudomyotonia (PMT) is an impairment of muscle relaxation induced by exercise that prevents animals from performing rapid movements. It has been described in Italian Chianina beef cattle [1], in Belgian Blue cattle (named muscular dystonia type II) [2] and, as a single case, in a Dutch improved Red and White cross-breed calf [3]. In muscular dystonia type II affected Belgian Blue cattle, Charlier et al [2] reported an ATP2A1 missense mutation (c.1675C>T) leading to an amino acid substitution The same mutation was reported to cause PMT in a single case of crossbred Dutch Improved Red cattle [3]

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