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

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• 作者：Mario Van Poucke^a ; ¹ ; ^{Mario.VanPoucke@UGent.be} ; An E. Vanhaesebrouck^b ; ^c ; ¹ ; Luc J. Peelman^a ; Luc Van Ham^b
• 关键词：Gene prediction error ; Myokymia ; Neuromyotonia ; Transcript variant ; Voltage-gated potassium channel
• 刊名：Neuromuscular Disorders
• 出版年：2012
• 期刊代码：203_09608966
• 类别：med
• 出版时间：June, 2012
• 卷：22
• 期：6
• 页码：558-565
• 文件大小：408 K

摘要

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.