背景:KCNJ10和CAPN1变异导致狗的“脊髓小脑”共济失调,但它们与广泛性肌强直和神经性肌强直的关系尚不清楚.
目的:为了研究KCNJ10和CAPN1与肌强直或神经强直的关系,伴有或不伴有脊髓小脑共济失调。
方法:33只患有脊髓小脑共济失调的患者犬,神经肌强直症,或这些迹象的组合。
方法:对一组临床诊断为脊髓小脑共济失调的狗进行遗传分析,肌强直或神经肌强直。KCNJ10c.627C>G和CAPN1c.34G>使用从血液样品中提取的DNA对KCNA1、KCNA2、KCNA6、KCNJ10和HINT1的变体和编码序列进行测序。
结果:二十四只杰克罗素梗,1杰克罗素梗十字架,对于KCNJ10c.627C>G变体,1只腊肠和1只脊髓小脑共济失调的混合品种是双等位基因(纯合)。其中21只狗有弱小症,神经肌强直,或者两者兼而有之。一个仅具有脊髓小脑性共济失调的帕森罗素梗对于CAPN1c.344G>A变体是双等位基因的。在1只患有共济失调的杰克罗素梗中没有发现两种变体,在3只杰克罗素梗和1只约克郡梗中也没有。在后5只狗中,在所研究的候选基因的编码序列中没有发现其它因果变异。
结论:KCNJ10c.627C>G变体,或很少CAPN1c.34G>A变体,被证实是脊髓小脑共济失调的因果变异。我们还报告了Dachshund品种中KCNJ10c.627C>G变体的存在。在仅患有肌强直和神经肌强直的狗中,未发现报道的基因变异。应调查其他遗传或免疫介导的原因,以解释这些病例的临床症状。
BACKGROUND: KCNJ10 and CAPN1 variants cause \"spinocerebellar\" ataxia in dogs, but their association with generalized myokymia and neuromyotonia remains unclear.
OBJECTIVE: To investigate the association between KCNJ10 and CAPN1 and myokymia or neuromyotonia, with or without concurrent spinocerebellar ataxia.
METHODS: Thirty-three client-owned dogs with spinocerebellar ataxia, myokymia neuromytonia, or a combination of these signs.
METHODS: Genetic analysis of a cohort of dogs clinically diagnosed with spinocerebellar ataxia, myokymia or neuromyotonia. KCNJ10 c.627C>G and CAPN1 c.344G>A variants and the coding sequence of KCNA1, KCNA2, KCNA6, KCNJ10 and HINT1 were sequenced using DNA extracted from blood samples.
RESULTS: Twenty-four Jack Russell terriers, 1 Jack Russell terrier cross, 1 Dachshund and 1 mixed breed with spinocerebellar ataxia were biallelic (homozygous) for the KCNJ10 c.627C>G variant. Twenty-one of those dogs had myokymia, neuromyotonia, or both. One Parson Russell terrier with spinocerebellar ataxia alone was biallelic for the CAPN1 c.344G>A variant. Neither variant was found in 1 Jack Russell terrier with ataxia alone, nor in 3 Jack Russell terriers and 1 Yorkshire terrier with myokymia and neuromyotonia alone. No other causal variants were found in the coding sequence of the investigated candidate genes in these latter 5 dogs.
CONCLUSIONS: The KCNJ10 c.627C>G variant, or rarely the CAPN1 c.344G>A variant, was confirmed to be the causal variant of spinocerebellar ataxia. We also report the presence of the KCNJ10 c.627C>G variant in the Dachshund breed. In dogs with myokymia and neuromyotonia alone the reported gene variants were not found. Other genetic or immune-mediated causes should be investigated to explain the clinical signs of these cases.