title: Pseudomyotonia in Romagnola cattle caused by novel ATP2A1 mutations.
abstract: BACKGROUND
  Bovine 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.
  
  
  RESULTS
  We 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.
  
  
  CONCLUSIONS
  Clinical, 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.
authors.affiliation: Institute of Genetics, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109a, 3001, Bern, Switzerland.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Murgiano
authors.forename: Roberta
authors.initials: R
authors.lastname: Sacchetto
authors.forename: Stefania
authors.initials: S
authors.lastname: Testoni
authors.forename: Tiziano
authors.initials: T
authors.lastname: Dorotea
authors.forename: Francesco
authors.initials: F
authors.lastname: Mascarello
authors.forename: Rocco
authors.initials: R
authors.lastname: Liguori
authors.forename: Arcangelo
authors.initials: A
authors.lastname: Gentile
authors.forename: Cord
authors.initials: C
authors.lastname: Drögemüller
mesh_terms: D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000201:enzymology / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005260:Female; D005838:Genotype; D006651:Histocytochemistry / Q000662:veterinary; D020386:Isaacs Syndrome / Q000201:enzymology / Q000235:genetics / Q000662:veterinary*; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology; D009154:Mutation; D010375:Pedigree; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D004247:DNA; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases