PPP5C pathogenic variant identified: a potential key to gaining insight into developmental and epileptic encephalopathy?
Abstract Background Emerging evidence suggesting a possible link between the PPP5C gene (protein phosphatase 5 catalytic subunit; OMIM#600658) and developmental and epileptic encephalopathy (DEE, OMIM#308350), although the clinical significance of pathogenic variants in this gene remains unclear. PP...
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SpringerOpen
2025-04-01
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| Series: | Molecular and Cellular Pediatrics |
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| Online Access: | https://doi.org/10.1186/s40348-025-00191-3 |
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| author | Raffaele Falsaperla Annamaria Sapuppo Xena Giada Pappalardo Roberta Rizzo Roberta Rocca Gaia Fusto Silvia Marino Vincenzo Sortino Lucia Saccuzzo Martino Ruggieri Marco Fichera |
| author_facet | Raffaele Falsaperla Annamaria Sapuppo Xena Giada Pappalardo Roberta Rizzo Roberta Rocca Gaia Fusto Silvia Marino Vincenzo Sortino Lucia Saccuzzo Martino Ruggieri Marco Fichera |
| author_sort | Raffaele Falsaperla |
| collection | DOAJ |
| description | Abstract Background Emerging evidence suggesting a possible link between the PPP5C gene (protein phosphatase 5 catalytic subunit; OMIM#600658) and developmental and epileptic encephalopathy (DEE, OMIM#308350), although the clinical significance of pathogenic variants in this gene remains unclear. PPP5C is a member of the protein phosphatase catalytic subunit family, which is involved in various signaling pathways governing cell growth, differentiation, and responses to hormonal signals or cellular stress. To date, only one case with a PPP5C variant has been reported, associated with a severe neurological phenotype, including microcephaly, failure to thrive, and early-onset seizures. Results We report a 12-year-old girl affected by epilepsy and learning disorders. At the age of five, she presented convulsive status epilepticus with respiratory failure at onset and she started anticonvulsant therapy with Levetiracetam with a significant improvement. Genetic analysis revealed a de novo heterozygous missense variant of PPP5C gene (c.202 C > T: p.Arg68Cys), which had not been previously described in the literature. Conclusion This case expands the phenotypic spectrum associated with PPP5C variants, highlighting the potential role of this gene inneurological disorders. Our findings may provide some valuable insights into the spectrum of phenotypic manifestations linked to this gene less investigated in neuropediatrics. |
| format | Article |
| id | doaj-art-83f5b63b16de489db00415bc0c014b9d |
| institution | DOAJ |
| issn | 2194-7791 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Molecular and Cellular Pediatrics |
| spelling | doaj-art-83f5b63b16de489db00415bc0c014b9d2025-08-20T03:04:51ZengSpringerOpenMolecular and Cellular Pediatrics2194-77912025-04-011211910.1186/s40348-025-00191-3PPP5C pathogenic variant identified: a potential key to gaining insight into developmental and epileptic encephalopathy?Raffaele Falsaperla0Annamaria Sapuppo1Xena Giada Pappalardo2Roberta Rizzo3Roberta Rocca4Gaia Fusto5Silvia Marino6Vincenzo Sortino7Lucia Saccuzzo8Martino Ruggieri9Marco Fichera10Department of Medical Science-Pediatrics, University of FerraraUnit of Pediatrics and Pediatric Emergency Department, Azienda Ospedaliero-Universitaria Policlinico “Rodolico-San Marco”, San Marco HospitalDepartment of Biomedical and Biotechnological Sciences (BIOMETEC), University of CataniaDepartment of Biomedical and Biotechnological Sciences (BIOMETEC), University of CataniaPostgraduate Training Program in Pediatrics, Department of Clinical and Experimental Medicine, University of CataniaDepartment of Biomedical and Biotechnological Sciences (BIOMETEC), University of CataniaUnit of Pediatrics and Pediatric Emergency Department, Azienda Ospedaliero-Universitaria Policlinico “Rodolico-San Marco”, San Marco HospitalUnit of Pediatrics and Pediatric Emergency Department, Azienda Ospedaliero-Universitaria Policlinico “Rodolico-San Marco”, San Marco HospitalDepartment of Biomedical and Biotechnological Sciences, Section of Clinical Biochemistry and Medical Genetics, University of CataniaUnit of Pediatric Clinic, Department of Clinica and Experimental Medicine, University of CataniaDepartment of Biomedical and Biotechnological Sciences, Section of Clinical Biochemistry and Medical Genetics, University of CataniaAbstract Background Emerging evidence suggesting a possible link between the PPP5C gene (protein phosphatase 5 catalytic subunit; OMIM#600658) and developmental and epileptic encephalopathy (DEE, OMIM#308350), although the clinical significance of pathogenic variants in this gene remains unclear. PPP5C is a member of the protein phosphatase catalytic subunit family, which is involved in various signaling pathways governing cell growth, differentiation, and responses to hormonal signals or cellular stress. To date, only one case with a PPP5C variant has been reported, associated with a severe neurological phenotype, including microcephaly, failure to thrive, and early-onset seizures. Results We report a 12-year-old girl affected by epilepsy and learning disorders. At the age of five, she presented convulsive status epilepticus with respiratory failure at onset and she started anticonvulsant therapy with Levetiracetam with a significant improvement. Genetic analysis revealed a de novo heterozygous missense variant of PPP5C gene (c.202 C > T: p.Arg68Cys), which had not been previously described in the literature. Conclusion This case expands the phenotypic spectrum associated with PPP5C variants, highlighting the potential role of this gene inneurological disorders. Our findings may provide some valuable insights into the spectrum of phenotypic manifestations linked to this gene less investigated in neuropediatrics.https://doi.org/10.1186/s40348-025-00191-3PPP5C (protein phosphatase 5 catalytic subunit)Developmental disordersStatus epilepticusDevelopmental and epileptic encephalopathy (DEE) |
| spellingShingle | Raffaele Falsaperla Annamaria Sapuppo Xena Giada Pappalardo Roberta Rizzo Roberta Rocca Gaia Fusto Silvia Marino Vincenzo Sortino Lucia Saccuzzo Martino Ruggieri Marco Fichera PPP5C pathogenic variant identified: a potential key to gaining insight into developmental and epileptic encephalopathy? Molecular and Cellular Pediatrics PPP5C (protein phosphatase 5 catalytic subunit) Developmental disorders Status epilepticus Developmental and epileptic encephalopathy (DEE) |
| title | PPP5C pathogenic variant identified: a potential key to gaining insight into developmental and epileptic encephalopathy? |
| title_full | PPP5C pathogenic variant identified: a potential key to gaining insight into developmental and epileptic encephalopathy? |
| title_fullStr | PPP5C pathogenic variant identified: a potential key to gaining insight into developmental and epileptic encephalopathy? |
| title_full_unstemmed | PPP5C pathogenic variant identified: a potential key to gaining insight into developmental and epileptic encephalopathy? |
| title_short | PPP5C pathogenic variant identified: a potential key to gaining insight into developmental and epileptic encephalopathy? |
| title_sort | ppp5c pathogenic variant identified a potential key to gaining insight into developmental and epileptic encephalopathy |
| topic | PPP5C (protein phosphatase 5 catalytic subunit) Developmental disorders Status epilepticus Developmental and epileptic encephalopathy (DEE) |
| url | https://doi.org/10.1186/s40348-025-00191-3 |
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