DNAJC5 gene

At least two mutations in the DNAJC5 gene have been found to cause Kufs disease type B. This condition is a type of neuronal ceroid lipofuscinosis (NCL) characterized by progressive problems with movement and a decline in intellectual function beginning in adulthood. One mutation replaces the protein building block (amino acid) leucine with the amino acid arginine at position 115 in the CSPα protein (written as L115R). The other mutation deletes the amino acid leucine at position 116 in the protein (written as L116del). These DNAJC5 gene mutations occur in one copy of the gene in each cell and lead to the production of an altered protein that does not associate with the synaptic vesicle, resulting in impaired nerve impulse transmission. Additionally, abnormal CSPα may attach (bind) to normal CSPα and prevent the protein from associating with synaptic vesicles, further impairing nerve impulse transmission.

In Kufs disease, fatty substances called lipopigments accumulate in the lysosomes of nerve cells (neurons) in the brain. These accumulations can result in cell dysfunction and eventually cause cell death. The progressive death of neurons contributes to the signs and symptoms of Kufs disease. However, it is unclear how mutations in the DNAJC5 gene are involved in the buildup of lipopigments and how impaired nerve impulse transmissions contribute to the signs and symptoms of Kufs disease.