Background
Cathepsin D is a lysosomal aspartic protease encoded by the CTSD gene. It plays important roles in many biological processes. Biallelic loss-of-function mutation of CTSD is considered a cause of CLN10 disease. CLN10 is a rare autosomal recessive disorder that is one of 14 types of neuronal ceroid lipofuscinoses (NCLs). To date, only a few cases of CLN10 and 12 disease-causing mutations have been reported worldwide.
Conclusion
These results suggest that the c.863A>G (p.Glu288Gly) homozygous variant is not a pathogenic variation, but a benign variant.
Methods
Exome sequencing was performed on a 15-year-old girl with pervasive brain developmental disorder. The effects of the identified variants were investigated through multiple functional experiments.
Results
There were no differences in mRNA and protein expression, intracellular localization, maturation, and proteolytic activity between the cells with the mutant CTSD gene and those with the wild-type CTSD gene.