PT - JOURNAL ARTICLE AU - An Vanhaesebrouck AU - Mario Van Poucke AU - Kimberley Stee AU - Luc Peelman AU - Luc Van Ham AU - Sofie F.M. Bhatti TI - Association of spinocerebellar ataxia related variants with myokymia and neuromyotonia in dogs AID - 10.1101/2022.11.17.516927 DP - 2022 Jan 01 TA - bioRxiv PG - 2022.11.17.516927 4099 - http://biorxiv.org/content/early/2022/11/18/2022.11.17.516927.short 4100 - http://biorxiv.org/content/early/2022/11/18/2022.11.17.516927.full AB - Background KCNJ10 and CAPN1 variants have been shown to cause spinocerebellar ataxia (SCA) in Jack Russell, Parson Russell and Fox terriers (JRT, PRT and FT). However, their association with the clinical manifestation of myokymia and neuromyotonia (M/NM), often reported alongside SCA, remains unclear.Aims To investigate the association between M/NM and SCA-related variants in 34 with SCA and/or M/NM affected dogs (30 JRTs; 1 PRT; 1 Yorkshire terrier, YT; 1 Dachshund; 1 crossbreed).Methods KCNJ10 XM_038448705.1:c.627C>G (p.(Ile209Met)) and CAPN1 XM_038425033.1:c.344G>A (p.(Cys115Tyr)) variants, and the complete coding sequence (CDS) of KCNA1, KCNA2, KCNA6, KCNJ10 and HINT1, were analysed via Sanger sequencing.Results The KCNJ10 c.627C>G variant was homozygously present in 16 JRTs, 1 Dachshund and 1 crossbreed with SCA and M/NM, and in 9 JRTs with SCA but without M/NM. The CAPN1 c.344G>A variant was homozygously present in 1 PRT with SCA but without M/NM. Both variants were not found in 2 JRTs with SCA but without M/NM, neither in 3 JRTs and 1 YT without SCA but with M/NM. No other causal variants were found in the coding sequence of the investigated candidate genes in these latter 6 dogs.Conclusions The KCNJ10 c.627C>G or CAPN1 c.344G>A variant was confirmed to be the causal variant in 28 of the 34 affected dogs (including 1 Dachshund with the KCNJ10 variant). The fact that 10 of these 28 dogs did not suffer from M/NM (all of them suffered from SCA) and that these variants were not found in 4 dogs suffering from M/NM without SCA, suggests that M/NM is caused by another genetic variant or that these patients suffer from an acquired (immune-mediated) syndrome, similar to humans. Another SCA-causing variant is probably also segregating in JRTs (but not in the CDS of the investigated candidate genes), because no causal variant was found in 2 JRTs suffering from SCA without M/NM.Competing Interest StatementThe authors have declared no competing interest.CAPN1calpain 1CDScoding sequenceEASTEpilepsy Ataxia Sensorineural Deafness TubulopathyFTFox terrierHINT1histidine triad nucleotide binding protein 1JRTJack Russell terrierKCNAxpotassium voltage-gated channel subfamily A member xKCNJ10potassium inwardly rectifying channel subfamily J member 10LOAlate onset ataxiaM/NMmyokymia and neuromyotoniaPCR-RFLPpolymerase chain reaction – restriction length polymorphismPRTParson Russell terrierSCAspinocerebellar ataxiaYTYorkshire terrier