A novel homozygous CLN6 Tyr142Cys variant in a nonconsanguineous family with Kufs disease.

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.

Case Description: 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.

Conclusion: 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.