Rohdin Cecilia, Gilliam Douglas, O'Leary Caroline A, O'Brien Dennis P, Coates Joan R, Johnson Gary S, Jäderlund Karin Hultin
Department of Clinical Sciences, Swedish University of Agricultural Sciences, SE-750 07, Uppsala, Sweden.
Anicura, Albano Small Animal Hospital, Rinkebyvägen 21, SE-182 36, Danderyd, Sweden.
Acta Vet Scand. 2015 May 23;57(1):26. doi: 10.1186/s13028-015-0115-1.
Hereditary ataxias with similar phenotypes were reported in the Smooth-Haired Fox Terrier, the Jack Russell Terrier and the Parson Russell Terrier. However, segregation analyses showed differing inheritance modes in these breeds. Recently, molecular genetic studies on the Russell group of terriers found independent mutations in KCNJ10 and CAPN1, each associated with a specific clinical subtype of inherited ataxia. The aim of this study was to clarify whether or not Smooth-Haired Fox Terriers with hereditary ataxia and dogs of other related breeds harbor either of the same mutations. A sub goal was to update the results of KCNJ10 genotyping in Russell group terriers.
Three Smooth-Haired Fox Terriers with hereditary ataxia and two Toy Fox Terriers with a similar phenotype were all homozygous for the KCNJ10 mutation. The same mutation was also found in a heterozygous state in clinically unaffected Tenterfield Terriers (n = 5) and, in agreement with previous studies, in Jack Russell Terriers, Parson Russell Terriers, and Russell Terriers.
A KCNJ10 mutation, previously associated with an autosomal recessive spinocerebellar ataxia in Jack Russell Terriers, Parson Russell Terriers, and Russell Terriers segregates in at least three more breeds descended from British hunting terriers. Ataxic members of two of these breeds, the Smooth-Haired Fox Terrier and the Toy Fox Terrier, were homozygous for the mutation, strengthening the likelihood that this genetic defect is indeed the causative mutation for the disease known as "hereditary ataxia" in Fox Terriers and "spinocerebellar ataxia with myokymia, seizures or both" in the Russell group of terriers.
在刚毛猎狐梗、杰克罗素梗和帕森罗素梗中报道了具有相似表型的遗传性共济失调。然而，分离分析显示这些品种的遗传模式不同。最近，对罗素梗犬组的分子遗传学研究发现KCNJ10和CAPN1存在独立突变，每个突变都与遗传性共济失调的特定临床亚型相关。本研究的目的是阐明患有遗传性共济失调的刚毛猎狐梗和其他相关品种的犬是否存在相同的突变。一个次要目标是更新罗素梗犬组中KCNJ10基因分型的结果。
三只患有遗传性共济失调的刚毛猎狐梗和两只具有相似表型的玩具猎狐梗均为KCNJ10突变的纯合子。在临床未受影响的滕特菲尔德梗犬（n = 5）中也发现了相同突变的杂合状态，并且与先前的研究一致，在杰克罗素梗、帕森罗素梗和罗素梗中也发现了该突变。
一种先前与杰克罗素梗、帕森罗素梗和罗素梗中的常染色体隐性遗传性脊髓小脑共济失调相关的KCNJ10突变，在至少另外三个源自英国狩猎梗犬的品种中分离。其中两个品种，即刚毛猎狐梗和玩具猎狐梗的共济失调成员为该突变的纯合子，这进一步证明了这种基因缺陷确实是猎狐梗中被称为“遗传性共济失调”以及罗素梗犬组中被称为“伴有肌纤维颤搐、癫痫发作或两者皆有的脊髓小脑共济失调”的疾病的致病突变。
