Beckers Evy, Bhatti Sofie F M, Van Poucke Mario, Polis Ingeborgh, Farnir Frédéric, Van Nieuwerburgh Filip, Mandigers Paul, Van Ham Luc, Peelman Luc, Broeckx Bart J G
Department of Veterinary and Biosciences, Faculty of Veterinary Medicine, Ghent University, 9820 Ghent, Belgium.
Small Animal Department, Faculty of Veterinary Medicine, Ghent University, 9820 Ghent, Belgium.
Animals (Basel). 2023 Feb 23;13(5):810. doi: 10.3390/ani13050810.
(1) Idiopathic epilepsy (IE) is thought to have a genetic cause in several dog breeds. However, only two causal variants have been identified to date, and few risk loci are known. No genetic studies have been conducted on IE in the Dutch partridge dog (DPD), and little has been reported on the epileptic phenotype in this breed. (2) Owner-filled questionnaires and diagnostic investigations were used to characterize IE in the DPD. A genome-wide association study (GWAS) involving 16 cases and 43 controls was performed, followed by sequencing of the coding sequence and splice site regions of a candidate gene within the associated region. Subsequent whole-exome sequencing (WES) of one family (including one IE-affected dog, both parents, and an IE-free sibling) was performed. (3) IE in the DPD has a broad range in terms of age at onset, frequency, and duration of epileptic seizures. Most dogs showed focal epileptic seizures evolving into generalized seizures. A new risk locus on chromosome 12 (BICF2G630119560; p = 4.4 × 10; p = 0.043) was identified through GWAS. Sequencing of the candidate gene revealed no variants of interest. No WES variants were located within the associated GWAS region. However, a variant in (chromosome 10; XM_038680630.1: c.689C > T) was discovered, and dogs homozygous for the variant (T/T) had an increased risk of developing IE (OR: 6.0; 95% CI: 1.6-22.6). This variant was identified as likely pathogenic according to ACMG guidelines. (4) Further research is necessary before the risk locus or variant can be used for breeding decisions.
(1) 特发性癫痫（IE）被认为在多个犬种中有遗传病因。然而，迄今为止仅鉴定出两个致病变异，且已知的风险位点很少。尚未对荷兰鹧鸪犬（DPD）的特发性癫痫进行基因研究，关于该品种癫痫表型的报道也很少。(2) 通过主人填写的问卷和诊断性调查来描述DPD中的特发性癫痫。进行了一项全基因组关联研究（GWAS），涉及16例病例和43例对照，随后对关联区域内一个候选基因的编码序列和剪接位点区域进行测序。随后对一个家系（包括一只受IE影响的犬、双亲以及一个未患IE的同胞）进行了全外显子测序（WES）。(3) DPD中的特发性癫痫在发病年龄、癫痫发作频率和持续时间方面范围很广。大多数犬表现为局灶性癫痫发作，随后演变为全身性发作。通过GWAS在12号染色体上鉴定出一个新的风险位点（BICF2G630119560；p = 4.4 × 10；p = 0.043）。对候选基因的测序未发现感兴趣的变异。WES变异不在关联的GWAS区域内。然而，发现了一个位于10号染色体上的变异（XM_038680630.1: c.689C > T），该变异纯合（T/T）的犬患IE的风险增加（比值比：6.0；95%置信区间：1.6 - 22.6）。根据美国医学遗传学与基因组学学会（ACMG）指南，该变异被确定为可能致病。(4) 在将风险位点或该变异用于繁殖决策之前，有必要进行进一步研究。
