Pseudomyotonia in Romagnola cattle caused by novel ATP2A1mutations

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.

Looking the Cow in the Eye: Deletion in the NID1 Gene Is Associated with Recessive Inherited Cataract in Romagnola Cattle

“…Romagnola is a local variety of beef cattle bred in north central Italy of about twenty thousand animals. Due to a significant level of inbreeding, the Romagnola breed recently has experienced outbreaks of two recessive diseases, namely paunch calf syndrome and pseudomyotonia, for which gene tests for eradication were developed after successful identification of the causative gene mutations [26] – [27] . During the fall of 2013 cataracts in four inbred juvenile Romagnola cattle were observed, prompting an in depth study to identify the causative mutation.…”

Detection of two non-synonymous SNPs in SLC45A2 on BTA20 as candidate causal mutations for oculocutaneous albinism in Braunvieh cattle

“…Moreover, there also exists the possibility that both mutations are needed to cause the albino phenotype. For example, a similar case of two disease-associated missense mutations that were found on a single haplotype was described for bovine congenital pseudomyotonia [ 52 ]. The relatively long common SNP-haplotype (47.61-Mb) that harbored the two candidate mutations, the perfect linkage disequilibrium between both mutations in the investigated samples, and their absence in all Braunvieh animals that were sampled outside of the case herd suggest that both the causal and the hitchhiking mutation were of recent origin, i.e.…”

Fourty-Four Years of Brody Disease: It is Time to Review

“…Analysis of diaphragm muscle displays increased fiber size variability and hypercontracted regions in scattered fibers suggesting that the absence of SERCA1 severely affects muscle functions [42]. Patients with Brody disease do not develop respiratory problems probably because Spontaneously occurring animals models of Brody disease have been recognized [43][44][45][46]. Congenital pseudomyotonia in Chianina and Romagnola cattle closely resembles Brody disease and is clinically characterized by exercise-induced muscle contractures and stiffness after fast movements [44].…”

“…Congenital pseudomyotonia in Chianina and Romagnola cattle closely resembles Brody disease and is clinically characterized by exercise-induced muscle contractures and stiffness after fast movements [44]. SR Ca 2+ -ATPase assay performed on miscrosomal fraction extracted from fast-twitch skeletal muscle demostrated a remarkable reduction in SERCA1 activity and genetic analysis revealed ATP2A1 mutations (c.491G>A, p.Arg164His; c.1675 C>T, p. Arg559Cys; c.632G>T, p. Gly211Val; c.857G>T, p.Gly284Val) that are transmitted with an autosomal recessive pattern [44][45][46].…”