The c.863A>G (p.Glu288Gly) variant of the CTSD gene is not associated with CLN10 disease

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. 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. Conclusion; These results suggest that the c.863A>G (p.Glu288Gly) homozygous variant is not a pathogenic variation, but a benign variant.

Automated summary

Biallelic loss-of-function mutation of the CTSD gene is considered a cause of CLN10 disease, but the pathogenicity of a specific variant remains controversial.