Molecular analysis in exons 1 and 2 of the tripeptidyl peptidase 1 (TPP1) gene on patients with neuronal ceroid lipofuscinosis type 2 (CLN2) in Indonesia

Neuronal ceroid lipofuscinosis type 2 (CLN2 disease) is an inborn error of metabolism due to the lack of catalytically-active tripeptidyl-peptidase (TPP1) enzyme encoded by the faulty human TPP1 gene. This study aims to identify the pathogenic variant that might be classified as the causal variant for CLN2 in Indonesia. This study focuses on the exon 1 to exon 2 since these regions are important sites for the synthesis of signal peptides of TPP1 enzyme. The subjects in this study were comprised of three patients confirmed with CLN2 disease and 20 healthy individuals as control. The detection of DNA variants was initiated by DNA extraction, primer design specific for the exons 1 and 2, DNA amplification by polymerase chain reaction (PCR) followed by visualization with gel electrophoresis, and continued by Sanger Sequencing. According to our analysis, we did not detect any clinically relevant variants in exons 1 and 2 of the TPP1 gene that might be the cause of CLN2 disease in our patients. However, we report c.17+16G>C variant in intron 1 of a healthy individual as we propose to classify this variant as benign. More research to detect disease-causing variants in three CLN2 patients in Indonesia needs to be continued to confirm the genetic diagnosis of CLN2 and discover the genetic etiology of CLN2 in our patients.