Abstract：
BACKGROUND: Neuronal ceroid lipofuscinoses are a genetically heterogeneous group of inherited lysosomal storage disorders. Kufs disease is the predominant form of neuronal ceroid lipofuscinosis in adults, but it\'s rare and challenging to diagnose.
METHODS: The proband initially presented with cognitive deterioration and parkinsonian traits. At 35, he was admitted to hospital following a tonic-clonic seizure. Brain magnetic resonance imaging showed atrophy of the cerebral cortex and cerebellum, enlarged ventricles, and thinned corpus callosum. The proband\'s younger brother and sister were also affected, and the clinical phenotype within the family was consistent. Whole-exome Sequencing of the proband revealed a novel homozygous mutation in CLN6 (NM_017882: c.425A > G, p. Tyr142Cys). Co-segregation analysis revealed that two other affected individuals carried a homozygous mutation at the same locus, with both parents exhibiting heterozygous mutations of c.425A > G.
CONCLUSIONS: Our study not only provides insights into the clinical presentation and development of the disease within the affected family but also expanded the mutational and phenotypical spectrum of the CLN6 gene.
METHODS: The proband initially presented with cognitive deterioration and parkinsonian traits. At 35, he was admitted to hospital following a tonic-clonic seizure. Brain magnetic resonance imaging showed atrophy of the cerebral cortex and cerebellum, enlarged ventricles, and thinned corpus callosum. The proband\'s younger brother and sister were also affected, and the clinical phenotype within the family was consistent. Whole-exome Sequencing of the proband revealed a novel homozygous mutation in CLN6 (NM_017882: c.425A > G, p. Tyr142Cys). Co-segregation analysis revealed that two other affected individuals carried a homozygous mutation at the same locus, with both parents exhibiting heterozygous mutations of c.425A > G.
CONCLUSIONS: Our study not only provides insights into the clinical presentation and development of the disease within the affected family but also expanded the mutational and phenotypical spectrum of the CLN6 gene.
摘要：
背景：神经元类脂褐素病是遗传性溶酶体贮积症的遗传异质性群体。Kufs病是成人神经元类脂褐菌病的主要形式，但它是罕见的和具有挑战性的诊断。
方法：先证者最初表现为认知退化和帕金森病特征。35岁时，他因强直阵挛性癫痫发作而入院。脑磁共振成像显示大脑皮层和小脑萎缩，扩大的心室，减少了胼胝体。先证者的弟弟和妹妹也受到影响，家族内的临床表型是一致的。先证者的全外显子组测序揭示了CLN6中的新纯合突变（NM_017882：c.425A>G，p.Tyr142Cys）。共分离分析显示，另外两个受影响的个体在同一基因座上携带纯合突变，父母双方都表现出c.425A>G的杂合突变。
结论：我们的研究不仅提供了对患病家族内疾病的临床表现和发展的见解，而且还扩展了CLN6基因的突变和表型谱。
方法：先证者最初表现为认知退化和帕金森病特征。35岁时，他因强直阵挛性癫痫发作而入院。脑磁共振成像显示大脑皮层和小脑萎缩，扩大的心室，减少了胼胝体。先证者的弟弟和妹妹也受到影响，家族内的临床表型是一致的。先证者的全外显子组测序揭示了CLN6中的新纯合突变（NM_017882：c.425A>G，p.Tyr142Cys）。共分离分析显示，另外两个受影响的个体在同一基因座上携带纯合突变，父母双方都表现出c.425A>G的杂合突变。
结论：我们的研究不仅提供了对患病家族内疾病的临床表现和发展的见解，而且还扩展了CLN6基因的突变和表型谱。
