Abstract：
Neuronal ceroid lipofuscinosis (NCL) is a group of neurodegenerative disorders that occur in humans, dogs, and several other species. NCL is characterised clinically by progressive deterioration of cognitive and motor function, epileptic seizures, and visual impairment. Most forms present early in life and eventually lead to premature death. Typical pathological changes include neuronal accumulation of autofluorescent, periodic acid-Schiff- and Sudan black B-positive lipopigments, as well as marked loss of neurons in the central nervous system. Here, we describe a 19-month-old Schapendoes dog, where clinical signs were indicative of lysosomal storage disease, which was corroborated by pathological findings consistent with NCL. Whole genome sequencing of the affected dog and both parents, followed by variant calling and visual inspection of known NCL genes, identified a missense variant in CLN6 (c.386T>C). The variant is located in a highly conserved region of the gene and predicted to be harmful, which supports a causal relationship. The identification of this novel CLN6 variant enables pre-breeding DNA-testing to prevent future cases of NCL6 in the Schapendoes breed, and presents a potential natural model for NCL6 in humans.
摘要：
神经元类脂褐菌病（NCL）是一组发生在人类中的神经退行性疾病，狗,和其他几个物种。NCL的临床特征是认知和运动功能的进行性恶化，癫痫发作,和视力障碍。大多数形式存在于生命早期，最终导致过早死亡。典型的病理变化包括自发荧光的神经元积累，高碘酸希夫和苏丹黑B阳性液体色素，以及中枢神经系统中神经元的明显丢失。这里,我们描述了一只19个月大的Schapendes狗，临床症状表明溶酶体贮积病，病理结果与NCL一致。受影响的狗和父母双方的全基因组测序，然后是已知NCL基因的变异调用和目视检查，在CLN6中发现了一个错义变体(c.386T>C)。该变体位于该基因的高度保守区域，并预测是有害的，这支持因果关系。这种新型CLN6变体的鉴定使得能够进行预育种DNA测试，以防止Schapendo品种中NCL6的未来病例，并提出了人类NCL6的潜在自然模型。
