Juvenile-Onset Kufs Disease in a Chinese Consanguineous Family due to CLN6 Mutation

Objective: The aim of this study was to identify the genetic cause of two cases of Kufs disease in the same family. The two affected individuals exhibited different levels of severity under magnetic resonance imaging (MRI). Methods: Whole-exome sequencing was performed on affected individuals, and the candidate gene was confirmed by Sanger sequencing. Western blot analysis was used to evaluate the level of expression of CLN6 protein in 239T cells. Results: We identified a novel homozygous mutation of the CLN6 gene (c.14G>T, p.Arg5Leu) in a consanguineous Chinese family in which two people had Kufs disease. Both patients exhibited seizures and progressive psychomotor decline and mental deterioration without visual impairment. They had different ages of onset, although they carried the same missense mutation. The affected female showed a pronounced abnormal MRI signal in the bilateral hippocampus, while her younger brother only showed a very slight abnormal signal. Further study showed that this missense mutation could decrease the level of expression of CLN6 protein. Conclusions: A novel homozygous mutation of the CLN6 gene was identified, and patients with the same mutation showed different ages of onset and different levels of severity under MRI. Significance: Our study established that the same CLN6 mutation could produce different phenotypes in patients, and it has expanded the mutational and phenotypical spectrum of the CLN6 gene.