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. Here, we report the novel variant c.863 A>G (p.Glu288Gly) of the CTSD gene in homozygous form, identified in a patient with an NCL‐like disorder. The effects of the variant on CatD expression, maturation, cellular localization, and enzymatic activity were studied. These results suggest that the c.863A>G (p.Glu288Gly) homozygous variant is not a pathogenic variation, but a benign variant.