Congenital pseudo-myotonia in Chianina and Romagnola cattle and congenital myotonia in a New Forest pony: genetic homologs of human muscular diseases

An inherited muscle disorder defined as “congenital pseudomyotonia” has been described in two important Italian cattle breeds Chianina and Romagnola and, as a single case, in a cross-breed calf in the Netherlands. Clinically the disorder is characterized by an exercise-induced muscle contraction. Cattle pseudomyotonia has been well characterized at both genetic and biochemical levels. By DNA sequencing of affected calves, we have provided evidence of mutations in ATP2A1 gene coding for sarco(endo)plasmic reticulum Ca2+-ATPase, isoform1 (SERCA1). Moreover we have demonstrated that cattle pathological muscles are characterized by a selective reduction in the level of SERCA1 expression. A New Forest foal has been evaluated for a muscular disorder: clinical findings include episodes of recumbency and stiffness with myotonic discharges on electromyography. The New Forest pony myotonia has been associated to a missense mutation in a well conserved domain of the equine chloride channel 1 (CLCN1) gene. The affected foal has been found to be homozygous and the mutation has revealed a recessive mode of inheritance within the reported pony family. On the basis of symptoms and of genetic confirmations, cattle pseudomyotonia has been defined as the true counterpart of human Brody disease, while the New Forest phenotype appeared related to human and goat congenital myotonia. Brody disease is a rare inherited disorder of skeletal muscle due to a SERCA1 deficiency, resulting from a defect of ATP2A1 gene. Human congenital myotonia results from recessive or dominant mutations of CLCN1 gene causing Becker’s or Thomsen’s disease, respectively. Our studies reflect the enormous potential of domestic animals to gain further insights into human medicine