# PPP5C pathogenic variant identified: a potential key to gaining insight into developmental and epileptic encephalopathy?

## TL;DR

A new PPP5C gene variant is linked to developmental and epileptic encephalopathy, expanding understanding of its role in neurological disorders.

## Contribution

The study reports a novel PPP5C variant in a patient with epilepsy and learning disorders, expanding the known phenotypic spectrum.

## Key findings

- A de novo PPP5C variant (c.202 C > T: p.Arg68Cys) was identified in a 12-year-old girl with epilepsy and learning disorders.
- The variant expands the phenotypic spectrum of PPP5C-related neurological disorders.
- The patient showed significant improvement with Levetiracetam therapy after convulsive status epilepticus.

## Abstract

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.

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.

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.