Case report: Analysis of novel compound heterozygous TPP1 variants in a Chinese patient with neuronal ceroid lipofuscinosis type 2
Neuronal ceroid lipofuscinosis type 2 (CLN2) is an autosomal recessive neurodegenerative disease caused by variants in the TPP1 gene that lead to the deficiency of the lysosomal enzyme tripeptidyl peptidase I (TPP1) activity. Herein, we report a rare case of CLN2 caused by two novel variants of TPP1...
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.937485/full |
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| author | Sui-Bing Miao Hui Guo De-Xian Kong Yuan-Yuan Zhao Shu-Hong Pan Yan Jiang Xing Gao Xiao-Hua Wu |
| author_facet | Sui-Bing Miao Hui Guo De-Xian Kong Yuan-Yuan Zhao Shu-Hong Pan Yan Jiang Xing Gao Xiao-Hua Wu |
| author_sort | Sui-Bing Miao |
| collection | DOAJ |
| description | Neuronal ceroid lipofuscinosis type 2 (CLN2) is an autosomal recessive neurodegenerative disease caused by variants in the TPP1 gene that lead to the deficiency of the lysosomal enzyme tripeptidyl peptidase I (TPP1) activity. Herein, we report a rare case of CLN2 caused by two novel variants of TPP1. The patient presented with seizures at onset, followed by progressive cognitive impairment, motor decline, and vision loss. Novel compound heterozygous variants, c.544_545del and c.230-3C>G, in TPP1 were identified by whole-exome sequencing. The variant assessment showed that the c.544_545del is a frameshift variant mediating mRNA decay and that c.230-3C>G is a splice variant generating aberrantly spliced TPP1 mRNA, as confirmed by a Splicing Reporter Minigene assay. In conclusion, clinical history, variant assessment, and molecular analyses demonstrate that the novel compound heterozygous variants are responsible for CLN2 disease in this patient. This study expands the mutation spectrum of TPP1. |
| first_indexed | 2024-04-11T11:08:23Z |
| format | Article |
| id | doaj.art-3c948be2c8754a43b36e84160f97ca6e |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-11T11:08:23Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-3c948be2c8754a43b36e84160f97ca6e2022-12-22T04:28:07ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-08-011310.3389/fgene.2022.937485937485Case report: Analysis of novel compound heterozygous TPP1 variants in a Chinese patient with neuronal ceroid lipofuscinosis type 2Sui-Bing Miao0Hui Guo1De-Xian Kong2Yuan-Yuan Zhao3Shu-Hong Pan4Yan Jiang5Xing Gao6Xiao-Hua Wu7Key Laboratory of Maternal and Fetal Medicine of Hebei Province, Institute of Reproductive Medicine of Shijiazhuang, The Fourth Hospital of Shijiazhuang Affiliated to Hebei Medical University, Shijiazhuang, ChinaDepartment of Obstetrics and Gynecology, The Fourth Affiliated Hospital of Hebei Medical University Shijiazhuang, Shijiazhuang, ChinaDepartment of Endocrinology, The Fourth Affiliated Hospital of Hebei Medical University Shijiazhuang, Shijiazhuang, ChinaKey Laboratory of Maternal and Fetal Medicine of Hebei Province, Institute of Reproductive Medicine of Shijiazhuang, The Fourth Hospital of Shijiazhuang Affiliated to Hebei Medical University, Shijiazhuang, ChinaKey Laboratory of Maternal and Fetal Medicine of Hebei Province, Institute of Reproductive Medicine of Shijiazhuang, The Fourth Hospital of Shijiazhuang Affiliated to Hebei Medical University, Shijiazhuang, ChinaCenter of Reproductive Medicine, The Fourth Hospital of Shijiazhuang Affiliated to Hebei Medical University, Shijiazhuang, ChinaCenter of Reproductive Medicine, The Fourth Hospital of Shijiazhuang Affiliated to Hebei Medical University, Shijiazhuang, ChinaKey Laboratory of Maternal and Fetal Medicine of Hebei Province, Institute of Reproductive Medicine of Shijiazhuang, The Fourth Hospital of Shijiazhuang Affiliated to Hebei Medical University, Shijiazhuang, ChinaNeuronal ceroid lipofuscinosis type 2 (CLN2) is an autosomal recessive neurodegenerative disease caused by variants in the TPP1 gene that lead to the deficiency of the lysosomal enzyme tripeptidyl peptidase I (TPP1) activity. Herein, we report a rare case of CLN2 caused by two novel variants of TPP1. The patient presented with seizures at onset, followed by progressive cognitive impairment, motor decline, and vision loss. Novel compound heterozygous variants, c.544_545del and c.230-3C>G, in TPP1 were identified by whole-exome sequencing. The variant assessment showed that the c.544_545del is a frameshift variant mediating mRNA decay and that c.230-3C>G is a splice variant generating aberrantly spliced TPP1 mRNA, as confirmed by a Splicing Reporter Minigene assay. In conclusion, clinical history, variant assessment, and molecular analyses demonstrate that the novel compound heterozygous variants are responsible for CLN2 disease in this patient. This study expands the mutation spectrum of TPP1.https://www.frontiersin.org/articles/10.3389/fgene.2022.937485/fullneuronal ceroid lipofuscinosis type 2 (CLN2)tripeptidyl peptidase I (TPP1)variantmolecular analysissplicing assay |
| spellingShingle | Sui-Bing Miao Hui Guo De-Xian Kong Yuan-Yuan Zhao Shu-Hong Pan Yan Jiang Xing Gao Xiao-Hua Wu Case report: Analysis of novel compound heterozygous TPP1 variants in a Chinese patient with neuronal ceroid lipofuscinosis type 2 Frontiers in Genetics neuronal ceroid lipofuscinosis type 2 (CLN2) tripeptidyl peptidase I (TPP1) variant molecular analysis splicing assay |
| title | Case report: Analysis of novel compound heterozygous TPP1 variants in a Chinese patient with neuronal ceroid lipofuscinosis type 2 |
| title_full | Case report: Analysis of novel compound heterozygous TPP1 variants in a Chinese patient with neuronal ceroid lipofuscinosis type 2 |
| title_fullStr | Case report: Analysis of novel compound heterozygous TPP1 variants in a Chinese patient with neuronal ceroid lipofuscinosis type 2 |
| title_full_unstemmed | Case report: Analysis of novel compound heterozygous TPP1 variants in a Chinese patient with neuronal ceroid lipofuscinosis type 2 |
| title_short | Case report: Analysis of novel compound heterozygous TPP1 variants in a Chinese patient with neuronal ceroid lipofuscinosis type 2 |
| title_sort | case report analysis of novel compound heterozygous tpp1 variants in a chinese patient with neuronal ceroid lipofuscinosis type 2 |
| topic | neuronal ceroid lipofuscinosis type 2 (CLN2) tripeptidyl peptidase I (TPP1) variant molecular analysis splicing assay |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.937485/full |
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