Case report: Analysis of novel compound heterozygous TPP1 variants in a Chinese patient with neuronal ceroid lipofuscinosis type 2

Front Genet. 2022 Aug 31;13:937485. doi: 10.3389/fgene.2022.937485.

PMID: 36118858

Sui-Bing Miao, Hui Guo, De-Xian Kong

Highlights: This article reports a rare case of neuronal ceroid lipofuscinosis type 2 (CLN2) caused by two novel variants of TPP1.

Abstract

Background: Lysosomal enzyme tripeptidyl peptidase I (TPP1) activity is impaired in neuronal ceroid lipofuscinosis type 2 (CLN2), an autosomal recessive neurodegenerative disorder brought on by variants in the TPP1 gene.

Objective and results: This study describes a unique instance of CLN2 brought on by two new TPP1 mutations. Seizures were the patient's initial presenting symptoms, which were then followed by gradual cognitive decline, motor deterioration, and vision loss. Through whole-exome sequencing, two new compound heterozygous variants in TPP1, c.544_545del and c.230-3C>G, were discovered. A Splicing Reporter Minigene test supported the variant assessment's findings that the frameshift variant c.544_545del mediates mRNA degradation and the splice variant c.230-3C>G results in aberrantly spliced TPP1 mRNA.

Conclusion: In conclusion, the clinical history, variant evaluation, and molecular tests show that the patient's CLN2 condition is caused by novel compound heterozygous variants. This investigation broadens the TPP1 mutation spectrum.

Keywords: Molecular analysis, neuronal ceroid lipofuscinosis type 2 (CLN2), splicing assay, tripeptidyl peptidase I (TPP1), variant