Experimental validation of in silico predicted KCNA1, KCNA2, KCNA6 and KCNQ2 genes for association studies of peripheral nerve hyperexcitability syndrome in Jack Russell Terriers

Neuromuscul Disord. 2012 Jun;22(6):558-65. doi: 10.1016/j.nmd.2012.01.008. Epub 2012 Feb 15.

Abstract

KCNA1, KCNA2, KCNA6 and KCNQ2 are associated with peripheral nerve hyperexcitability in humans. In order to determine if these genes are also involved in Jack Russell Terriers with a similar syndrome characterized by myokymia and neuromyotonia, their predicted canine orthologs were first validated experimentally. They were found either incompletely or even incorrectly annotated, mainly due to gaps in the canine genomic sequence and insufficient transcript data. Canine KCNQ2 was found to contain 20 coding exons, of which three are not described in humans. It encodes for at least 14 different transcript variants in the frontal cortex of a single dog, of which only four are also described in humans. Mutation detection in Jack Russell Terriers diagnosed with peripheral nerve hyperexcitability revealed no pathogenetic relevant structural mutations. However, the four missense sequence variations and the 14 transcript variants of KCNQ2 will contribute to the study of the functional diversity of voltage-gated potassium channels.

MeSH terms

  • Animals
  • Dog Diseases / genetics*
  • Dogs
  • Genetic Association Studies
  • Isaacs Syndrome / genetics
  • Isaacs Syndrome / veterinary
  • KCNQ2 Potassium Channel / genetics*
  • Kv1.1 Potassium Channel / genetics*
  • Kv1.2 Potassium Channel / genetics*
  • Kv1.6 Potassium Channel / genetics*
  • Mutation
  • Myokymia / genetics
  • Myokymia / veterinary
  • Peripheral Nervous System Diseases / genetics
  • Peripheral Nervous System Diseases / veterinary*

Substances

  • KCNQ2 Potassium Channel
  • Kv1.2 Potassium Channel
  • Kv1.6 Potassium Channel
  • Kv1.1 Potassium Channel